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1.
J Clin Med ; 11(13)2022 Jun 21.
Article in English | MEDLINE | ID: covidwho-1934146

ABSTRACT

BACKGROUND: Severe pneumonia caused by coronavirus disease 2019 (COVID-19) is characterized by inflammatory lung injury, progressive parenchymal stiffening and consolidation, alveolar and airway collapse, altered vascular permeability, diffuse alveolar damage, and surfactant deficiency. COVID-19 causes both pneumonia and acute respiratory distress syndrome (COVID-19 ARDS). COVID-19 ARDS is characterized by severe refractory hypoxemia and high mortality. Despite extensive research, the treatment of COVID-19 ARDS is far from satisfactory. Some treatments are recommended for exhibiting some clinically positive impacts on COVID-19 patients although there are already several drugs in clinical trials, some of which are already demonstrating promising results in addressing COVID-19. Few studies have demonstrated beneficial effects in non-COVID-19 ARDS treatment of exogenous surfactant, and there is no evidence-based, proven method for the procedure of surfactant administration. AIM: The aim of this work is to underline the key role of ATII cells and reduced surfactant levels in COVID-19 ARDS and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS, providing insights for future research. METHODS: In this article, we describe and support via the literature the decision to administer large volumes of surfactant to two patients via bronchoalveolar lavage to maximize its distribution in the respiratory tract. RESULTS: In this study, we report on two cases of COVID-19 ARDS in patients who have been successfully treated with diluted surfactants by bronchoalveolar lavage, followed by a low-dose bolus of surfactant. CONCLUSION: Combining the administration of diluted, exogenous pulmonary surfactant via bronchoalveolar lavage along with the standard therapy for SARS-CoV-2-induced ARDS may be a promising way of improving the management of ARDS.

2.
J Clin Med ; 11(11)2022 May 24.
Article in English | MEDLINE | ID: covidwho-1911411

ABSTRACT

BACKGROUND: Glucocorticoids (GCs) have been shown to reduce mortality and the need for invasive mechanical ventilation (IMV) in SARS-CoV-2-induced acute respiratory distress syndrome (ARDS). It has been suggested that serum cytokines levels are markers of disease severity in ARDS, although there is only limited evidence of a relationship between the longitudinal cytokine profile and clinical outcomes in patients with SARS-CoV-2-induced ARDS treated with GC. METHODS: We conducted a single-center observational study to investigate serial plasma cytokine levels in 17 patients supported with non-invasive ventilation (NIV) in order to compare the response in five patients who progressed to IMV versus 12 patients who continued with NIV alone. All patients received methylprednisolone 80 mg/day continuous infusion until clinical improvement. RESULTS: The study groups were comparable at baseline. All patients survived. Although IL-6 was higher in the NIV group at baseline, several cytokines were significantly higher in the IMV group on day 7 (IL-6, IL-8, IL-9, G-CSF, IP-10, MCP-1, MIP-1α) and 14 (IL-6, IL-8, IL-17, G-CSF, MIP-1α, RANTES). No significant differences were observed between groups on day 28. CONCLUSIONS: Patients in the IMV group had higher inflammation levels at intubation than the NIV group, which may indicate a higher resistance to glucocorticoids. Higher GC doses or a longer treatment duration in these patients might have allowed for a better control of inflammation and a better outcome. Further studies are required to define the prognostic value of cytokine patterns, in terms of both GC treatment tailoring and timely initiation of IMV.

3.
Journal of Clinical Medicine ; 11(13):3577, 2022.
Article in English | MDPI | ID: covidwho-1894201

ABSTRACT

Background: Severe pneumonia caused by coronavirus disease 2019 (COVID-19) is characterized by inflammatory lung injury, progressive parenchymal stiffening and consolidation, alveolar and airway collapse, altered vascular permeability, diffuse alveolar damage, and surfactant deficiency. COVID-19 causes both pneumonia and acute respiratory distress syndrome (COVID-19 ARDS). COVID-19 ARDS is characterized by severe refractory hypoxemia and high mortality. Despite extensive research, the treatment of COVID-19 ARDS is far from satisfactory. Some treatments are recommended for exhibiting some clinically positive impacts on COVID-19 patients although there are already several drugs in clinical trials, some of which are already demonstrating promising results in addressing COVID-19. Few studies have demonstrated beneficial effects in non-COVID-19 ARDS treatment of exogenous surfactant, and there is no evidence-based, proven method for the procedure of surfactant administration. Aim: The aim of this work is to underline the key role of ATII cells and reduced surfactant levels in COVID-19 ARDS and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS, providing insights for future research. Methods: In this article, we describe and support via the literature the decision to administer large volumes of surfactant to two patients via bronchoalveolar lavage to maximize its distribution in the respiratory tract. Results: In this study, we report on two cases of COVID-19 ARDS in patients who have been successfully treated with diluted surfactants by bronchoalveolar lavage, followed by a low-dose bolus of surfactant. Conclusion: Combining the administration of diluted, exogenous pulmonary surfactant via bronchoalveolar lavage along with the standard therapy for SARS-COV-2-induced ARDS may be a promising way of improving the management of ARDS.

4.
Journal of Clinical Medicine ; 11(11):2951, 2022.
Article in English | MDPI | ID: covidwho-1857696

ABSTRACT

Background. Glucocorticoids (GCs) have been shown to reduce mortality and the need for invasive mechanical ventilation (IMV) in SARS-CoV-2-induced acute respiratory distress syndrome (ARDS). It has been suggested that serum cytokines levels are markers of disease severity in ARDS, although there is only limited evidence of a relationship between the longitudinal cytokine profile and clinical outcomes in patients with SARS-CoV-2-induced ARDS treated with GC. Methods. We conducted a single-center observational study to investigate serial plasma cytokine levels in 17 patients supported with non-invasive ventilation (NIV) in order to compare the response in five patients who progressed to IMV versus 12 patients who continued with NIV alone. All patients received methylprednisolone 80 mg/day continuous infusion until clinical improvement. Results. The study groups were comparable at baseline. All patients survived. Although IL-6 was higher in the NIV group at baseline, several cytokines were significantly higher in the IMV group on day 7 (IL-6, IL-8, IL-9, G-CSF, IP-10, MCP-1, MIP-1α) and 14 (IL-6, IL-8, IL-17, G-CSF, MIP-1α, RANTES). No significant differences were observed between groups on day 28. Conclusions. Patients in the IMV group had higher inflammation levels at intubation than the NIV group, which may indicate a higher resistance to glucocorticoids. Higher GC doses or a longer treatment duration in these patients might have allowed for a better control of inflammation and a better outcome. Further studies are required to define the prognostic value of cytokine patterns, in terms of both GC treatment tailoring and timely initiation of IMV.

5.
Tomography ; 8(3): 1221-1227, 2022 04 24.
Article in English | MEDLINE | ID: covidwho-1810207

ABSTRACT

PURPOSE: To assess the diagnostic accuracy of traditional chest X-ray (CXR) and digital tomosynthesis (DTS) compared to computed tomography (CT) in detecting pulmonary interstitial changes in patients having recovered from severe COVID-19. MATERIALS AND METHODS: This was a retrospective observational study, and received local ethics committee approval. Patients suspected of having COVID-19 pneumonia upon emergency department admission between 1 March and 31 August 2020, and who underwent CXR followed by DTS and CT, were considered. Inclusion criteria were as follows: (1) patients with previous SARS-CoV-2 infection proven by a positive RT-PCR on nasopharyngeal swabs performed upon admission to the hospital, and with complete clinical recovery; (2) a diagnosis of SARS-CoV-2-related ARDS, according to the Berlin criteria, during hospitalization; (3) no recent history of other lung disease; and (4) complete imaging follow-up by CXR, DTS, and CT for at least 6 months and up to one year. Analysis of DTS images was carried out independently by two radiologists with 16 and 10 years of experience in chest imaging, respectively. The following findings were evaluated: (1) ground-glass opacities (GGOs); (2) air-space consolidations with or without air bronchogram; (3) reticulations; and (4) linear consolidation. Indicators of diagnostic performance of RX and digital tomosynthesis were calculated using CT as a reference. All data were analyzed using R statistical software (version 4.0.2, 2020). RESULTS: Out of 44 patients initially included, 25 patients (17 M/8 F), with a mean age of 64 years (standard deviation (SD): 12), met the criteria and were included. The overall average numbers of findings confirmed by CT were GGOs in 11 patients, lung consolidations in 8 patients, 7 lung interstitial reticulations, and linear consolidation in 20 patients. DTS showed a significantly higher diagnostic accuracy compared to CXR in recognizing interstitial lung abnormalities-especially GGOs (p = 0.0412) and linear consolidations (p = 0.0009). The average dose for chest X-ray was 0.10 mSv (0.07-0.32), for DTS was 1.03 mSv (0.74-2.00), and for CT scan was 3 mSv. CONCLUSIONS: According to our results, DTS possesses a high diagnostic accuracy, compared with CXR, in revealing lung fibrotic changes in patients who have recovered from COVID-19 pneumonia.


Subject(s)
COVID-19 , Pulmonary Fibrosis , COVID-19/diagnostic imaging , Humans , Middle Aged , Radiographic Image Enhancement/methods , Radiography, Thoracic/methods , SARS-CoV-2
6.
J Clin Med ; 11(6)2022 Mar 19.
Article in English | MEDLINE | ID: covidwho-1760681

ABSTRACT

The latest guidelines for the hospital care of patients affected by coronavirus disease 2019 (COVID-19)-related acute respiratory failure have moved towards the widely accepted use of noninvasive respiratory support (NIRS) as opposed to early intubation at the pandemic onset. The establishment of severe COVID-19 pneumonia goes through different pathophysiological phases that partially resemble typical acute respiratory distress syndrome (ARDS) and have been categorized into different clinical-radiological phenotypes. These can variably benefit on the application of external positive end-expiratory pressure (PEEP) during noninvasive mechanical ventilation, mainly due to variable levels of lung recruitment ability and lung compliance during different phases of the disease. A growing body of evidence suggests that intense respiratory effort producing excessive negative pleural pressure swings (Ppl) plays a critical role in the onset and progression of lung and diaphragm damage in patients treated with noninvasive respiratory support. Routine respiratory monitoring is mandatory to avoid the nasty continuation of NIRS in patients who are at higher risk for respiratory deterioration and could benefit from early initiation of invasive mechanical ventilation instead. Here we propose different monitoring methods both in the clinical and experimental settings adapted for this purpose, although further research is required to allow their extensive application in clinical practice. We reviewed the needs and available tools for clinical-physiological monitoring that aims at optimizing the ventilatory management of patients affected by acute respiratory distress syndrome due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

7.
PLoS One ; 17(3): e0265202, 2022.
Article in English | MEDLINE | ID: covidwho-1753195

ABSTRACT

BACKGROUND: Non-invasive ventilation (NIV) has been increasingly used in COVID-19 patients. The limited physiological monitoring and the unavailability of respiratory mechanic measures, usually obtainable during invasive ventilation, is a limitation of NIV for ARDS and COVID-19 patients management. OBJECTIVES: This pilot study was aimed to evaluate the feasibility of non-invasively monitoring respiratory mechanics by oscillometry in COVID-19 patients with moderate-severe acute respiratory distress syndrome (ARDS) receiving NIV. METHOD: 15 COVID-19 patients affected by moderate-severe ARDS at the RICU (Respiratory Intensive Care Unit) of the University hospital of Cattinara, Trieste, Italy were recruited. Patients underwent oscillometry tests during short periods of spontaneous breathing between NIV sessions. RESULTS: Oscillometry proved to be feasible, reproducible and well-tolerated by patients. At admission, 8 of the 15 patients showed oscillometry parameters within the normal range which further slightly improved before discharge. At discharge, four patients had still abnormal respiratory mechanics, not exclusively linked to pre-existing respiratory comorbidities. Lung mechanics parameters were not correlated with oxygenation. CONCLUSIONS: Our results suggest that lung mechanics provide complementary information for improving patients phenotyping and personalisation of treatments during NIV in COVID 19 patients, especially in the presence of respiratory comorbidities where deterioration of lung mechanics may be less coupled with changes in oxygenation and more difficult to identify. Oscillometry may provide a valuable tool for monitoring lung mechanics in COVID 19 patients receiving NIV.


Subject(s)
COVID-19/therapy , Lung/physiopathology , Noninvasive Ventilation/methods , Oscillometry/methods , Respiratory Distress Syndrome/virology , Adult , Aged , COVID-19/physiopathology , Feasibility Studies , Female , Humans , Italy , Male , Middle Aged , Pilot Projects , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , Respiratory Mechanics , Retrospective Studies
8.
ERJ Open Res ; 7(3)2021 Jul.
Article in English | MEDLINE | ID: covidwho-1526592

ABSTRACT

Pneumomediastinum is a rare complication of ARDS but is more common during #COVID19. The fibrous hyaline degeneration of the tracheal rings seen in this autoptic series is an original observation that has not been previously described in COVID-19 patients. https://bit.ly/3vxTQde.

9.
Med Lav ; 112(5): 331-339, 2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1498269

ABSTRACT

BACKGROUND: the sensitivity and specificity of a rapid antibody test were investigated for the screening of healthcare workers. METHODS: the serum of 389 health care workers exposed to COVID-19 patients or with symptoms, were analysed. All workers underwent monthly the screening for SARS-CoV-2 with detection of viral RNA in nasopharyngeal swabs by RT-PCR. IgG antibody detection in serum was performed by Chemiluminescence Immunoassay (CLIA) and by the Rapid test (KHB diagnostic kit for SARS CoV-2 IgM/IgG antibody after a median of 7.6 weeks (25°-75° percentiles 6.6-11.5). RESULTS: the rapid test resulted positive in 31/132 (23.5%), 16/135 (11.8%) and 0/122 cases in COVID-19 positive individuals, in those with only SARS-CoV-2 IgG antibodies and in those negative for both tests, respectively. Sensitivity was 17.6% (CI95% 13.2-22.7) and 23.5% (CI95% 16.5-31.6), and specificity was 100% (CI95% 97-100) and 100% (CI95% 97-100) considering Rapid test vs CLIA IgG or Rapid test vs SARS-CoV-2 positive RNA detection, respectively. CONCLUSION: the KHB Rapid test is not suitable for the screening of workers with previous COVID-19 infection.


Subject(s)
COVID-19 , COVID-19 Testing , Health Personnel , Humans , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2 , Sensitivity and Specificity
10.
Encyclopedia of Respiratory Medicine (Second Edition) ; : 10-17, 2022.
Article in English | ScienceDirect | ID: covidwho-1415139

ABSTRACT

The alveolar epithelium is a thin continuous liquid lining layer primarily composed of two types of epithelial cells, i.e., alveolar type I (ATI) and alveolar type II (ATII) cells. ATI cells have a broad flattened morphology and cover about 95% of the gas exchange surface of the lung. Whilst, ATIIs are small cuboidal cells with characteristic lamellar inclusions and apical microvilli that line the remainder of the alveolus (about 5%). ATII cells make and secrete a pulmonary surfactant, which reduces the surface tension in the alveoli preventing alveolar collapse during respiration and reducing the energy required to inflate the lungs, thereby increasing pulmonary compliance. These cells also transport ions from the apical to the basolateral surface so as to keep the alveoli relatively fluid free and have roles in the innate immune response. Importantly, they are the progenitor cells for the alveolar epithelium in the adult lung. Having a very thin cytoplasm, a limited number of mitochondria and covering a higher surface area, ATI cells are easily damaged during lung injury, after which they are replaced by ATII cells through the alveolar epithelium regeneration process. Despite ATII cells are considered an essential part of this process, numerous interstitial lung diseases are characterized by hyperplastic ATIIs: in fact, they may also contribute to the fibroproliferative reaction by secreting a number of growth factors and proinflammatory molecules.

11.
Int J Mol Sci ; 22(5)2021 Mar 04.
Article in English | MEDLINE | ID: covidwho-1389392

ABSTRACT

Alveolar type II (ATII) cells are a key structure of the distal lung epithelium, where they exert their innate immune response and serve as progenitors of alveolar type I (ATI) cells, contributing to alveolar epithelial repair and regeneration. In the healthy lung, ATII cells coordinate the host defense mechanisms, not only generating a restrictive alveolar epithelial barrier, but also orchestrating host defense mechanisms and secreting surfactant proteins, which are important in lung protection against pathogen exposure. Moreover, surfactant proteins help to maintain homeostasis in the distal lung and reduce surface tension at the pulmonary air-liquid interface, thereby preventing atelectasis and reducing the work of breathing. ATII cells may also contribute to the fibroproliferative reaction by secreting growth factors and proinflammatory molecules after damage. Indeed, various acute and chronic diseases are associated with intensive inflammation. These include oedema, acute respiratory distress syndrome, fibrosis and numerous interstitial lung diseases, and are characterized by hyperplastic ATII cells which are considered an essential part of the epithelialization process and, consequently, wound healing. The aim of this review is that of revising the physiologic and pathologic role ATII cells play in pulmonary diseases, as, despite what has been learnt in the last few decades of research, the origin, phenotypic regulation and crosstalk of these cells still remain, in part, a mystery.


Subject(s)
Alveolar Epithelial Cells/pathology , Alveolar Epithelial Cells/physiology , Lung Diseases/physiopathology , Lung/physiology , Alveolar Epithelial Cells/cytology , Animals , COVID-19/physiopathology , Humans , Immunity, Innate , Ions/metabolism , Lung/anatomy & histology , Lung Diseases/etiology , Lung Diseases/pathology , Pulmonary Surfactant-Associated Proteins/metabolism , Regeneration
14.
Open Forum Infect Dis ; 7(10): ofaa421, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-756944

ABSTRACT

BACKGROUND: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. METHODS: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. RESULTS: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ±â€…9.0 vs 17.5 ±â€…12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). CONCLUSION: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.

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