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Article ; Online: What remains in the pulmonary tissue after acute COVID-19?

Duarte-Neto, Amaro Nunes / Dolhnikoff, Marisa

Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia

2022 Volume 48, Issue 3, Page(s) e20220209

MeSH term(s)	COVID-19 ; Humans ; Lung ; SARS-CoV-2
Language	Portuguese
Publishing date	2022-07-08
Publishing country	Brazil
Document type	Editorial ; Comment
ZDB-ID	2223157-2
ISSN	1806-3756 ; 1806-3713
ISSN (online)	1806-3756
ISSN	1806-3713
DOI	10.36416/1806-3756/e20220209
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Article: Younger age is associated with cardiovascular pathological phenotype of severe COVID-19 at autopsy.

Giugni, Fernando R / Duarte-Neto, Amaro N / da Silva, Luiz Fernando F / Monteiro, Renata A A / Mauad, Thais / Saldiva, Paulo H N / Dolhnikoff, Marisa

Frontiers in medicine

2024 Volume 10, Page(s) 1327415

Abstract: Introduction: COVID-19 affects patients of all ages. There are few autopsy studies focusing on the younger population. We assessed an autopsy cohort aiming to understand how age influences pathological outcomes in fatal COVID-19.: Methods: This study ...

Abstract	Introduction: COVID-19 affects patients of all ages. There are few autopsy studies focusing on the younger population. We assessed an autopsy cohort aiming to understand how age influences pathological outcomes in fatal COVID-19. Methods: This study included autopsied patients, aged 6 months to 83 years, with confirmed COVID-19 in 2020-2021. We collected tissue samples from deceased patients using a minimally invasive autopsy protocol and assessed pathological data following a systematic approach. Results: Eighty-six patients were included, with a median age of 55 years (IQR 32.3-66.0). We showed that age was significantly lower in patients with acute heart ischemia ( Conclusion: We showed that age modulates pathological outcomes in fatal COVID-19. Younger age is associated with cardiovascular abnormalities and older age with pulmonary findings.
Language	English
Publishing date	2024-01-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1327415
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Article ; Online: Lung tissue expression of epithelial injury markers is associated with acute lung injury severity but does not discriminate sepsis from ARDS.

de Souza Xavier Costa, Natália / da Costa Sigrist, Giovana / Schalch, Alexandre Santos / Belotti, Luciano / Dolhnikoff, Marisa / da Silva, Luiz Fernando Ferraz

Respiratory research

2024 Volume 25, Issue 1, Page(s) 129

Abstract: Background: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS ... ...

Abstract	Background: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity. Methods: We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis. Results: We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO Conclusions: Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients.
MeSH term(s)	Humans ; Elafin ; Pulmonary Surfactant-Associated Protein D ; Lung ; Respiratory Distress Syndrome/diagnosis ; Acute Lung Injury ; Sepsis/diagnosis ; Sepsis/complications
Chemical Substances	Elafin ; Pulmonary Surfactant-Associated Protein D
Language	English
Publishing date	2024-03-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-024-02761-x
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Article ; Online: Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis.

Mendonça, Lígia Pelosi / Costa, Natalia de Souza Xavier / do Nascimento, Ellen Caroline Toledo / de Oliveira, Martina Rodrigues / de Carvalho, Carlos Roberto Ribeiro / Baldi, Bruno Guedes / Dolhnikoff, Marisa

BMC pulmonary medicine

2024 Volume 24, Issue 1, Page(s) 22

Abstract: Background: Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies ... ...

Abstract	Background: Lymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS). Methods: Thirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-β expression, and infiltration of LAM cells and inflammatory cells within the small airway walls. Results: The age of patients with LAM was 39 ± 8 years, with FEV1 and DLCO of 62 ± 30% predicted and 62 ± 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 ≤ 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content. Conclusion: LAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).
MeSH term(s)	Humans ; Female ; Adult ; Middle Aged ; Lymphangioleiomyomatosis ; Airway Remodeling ; Biopsy ; Collagen ; Transforming Growth Factor beta
Chemical Substances	Collagen (9007-34-5) ; Transforming Growth Factor beta
Language	English
Publishing date	2024-01-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2059871-3
ISSN	1471-2466 ; 1471-2466
ISSN (online)	1471-2466
ISSN	1471-2466
DOI	10.1186/s12890-023-02837-2
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Article ; Online: Transmission electron microscopy reveals the presence of SARS-CoV-2 in human spermatozoa associated with an ETosis-like response.

Hallak, Jorge / Caldini, Elia G / Teixeira, Thiago A / Correa, Maria Cassia Mendes / Duarte-Neto, Amaro N / Zambrano, Fabiola / Taubert, Anja / Hermosilla, Carlos / Drevet, Joël R / Dolhnikoff, Marisa / Sanchez, Raul / Saldiva, Paulo H N

Andrology

2024

Abstract: Background: Severe acute syndrome coronavirus 2 can invade a variety of tissues, including the testis. Even though this virus is scarcely found in human semen polymerase chain reaction tests, autopsy studies confirm the viral presence in all testicular ... ...

Abstract	Background: Severe acute syndrome coronavirus 2 can invade a variety of tissues, including the testis. Even though this virus is scarcely found in human semen polymerase chain reaction tests, autopsy studies confirm the viral presence in all testicular cell types, including spermatozoa and spermatids. Objective: To investigate whether the severe acute syndrome coronavirus 2 is present inside the spermatozoa of negative polymerase chain reaction-infected men up to 3 months after hospital discharge. Materials and methods: This cross-sectional study included 13 confirmed moderate-to-severe COVID-19 patients enrolled 30-90 days after the diagnosis. Semen samples were obtained and examined with real-time polymerase chain reaction for RNA detection and by transmission electron microscopy. Results: In moderate-to-severe clinical scenarios, we identified the severe acute syndrome coronavirus 2 inside spermatozoa in nine of 13 patients up to 90 days after discharge from the hospital. Moreover, some DNA-based extracellular traps were reported in all studied specimens. Discussion and conclusion: Although severe acute syndrome coronavirus 2 was not present in the infected men's semen, it was intracellularly present in the spermatozoa till 3 months after hospital discharge. The Electron microscopy (EM) findings also suggest that spermatozoa produce nuclear DNA-based extracellular traps, probably in a cell-free DNA-dependent manner, similar to those previously described in the systemic inflammatory response to COVID-19. In moderate-to-severe cases, the blood-testes barrier grants little defence against different pathogenic viruses, including the severe acute syndrome coronavirus 2. The virus could also use the epididymis as a post-testicular route to bind and fuse to the mature spermatozoon and possibly accomplish the reverse transcription of the single-stranded viral RNA into proviral DNA. These mechanisms can elicit extracellular cell-free DNA formation. The potential implications of our findings for assisted conception must be addressed, and the evolutionary history of DNA-based extracellular traps as preserved ammunition in animals' innate defence might improve our understanding of the severe acute syndrome coronavirus 2 pathophysiology in the testis and spermatozoa.
Language	English
Publishing date	2024-03-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2696108-8
ISSN	2047-2927 ; 2047-2919
ISSN (online)	2047-2927
ISSN	2047-2919
DOI	10.1111/andr.13612
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Article ; Online: Effect of Hypertonic Saline Solution on the Ventilatory Mechanics of Lungs Donated After Brain Death.

Ruiz, Liliane Moreira / de Oliveira Braga, Karina Andrighetti / Nepomuceno, Natalia Aparecida / Correia, Aristides Tadeu / Ribeiro de Carvalho, Guilherme Henrique / Vilela, Vanessa Sana / Dolhnikoff, Marisa / Pêgo-Fernandes, Paulo Manuel

The Journal of surgical research

2024 Volume 298, Page(s) 109–118

Abstract: Introduction: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in ... ...

Abstract	Introduction: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in the inflammatory activity of the lungs of rats subjected to BD. Methods: Wistar rats were divided into four groups: control, n = 10: intact rats subjected to extraction of the heart-lung block; BD, n = 8 (BD): rats treated with isotonic saline solution (4 mL/kg) immediately after BD; hypertonic saline 0 h, n = 9 (Hip.0'): rats treated with HSS (4 mL/kg) immediately after BD; and hypertonic saline 1 h, n = 9 (Hip.60'), rats treated with HSS (4 mL/kg) 60 min after BD. The hemodynamic characteristics, gas exchange, VMs, inflammatory mediators, and histopathological evaluation of the lung were evaluated over 240 min of BD. Results: In VMs, we observed increased airway resistance, tissue resistance, tissue elastance, and respiratory system compliance in the BD group (P < 0.037), while the treated groups showed no impairment over time (P > 0.05). In the histological analysis, the BD group showed a greater area of perivascular edema and a higher neutrophil count than the control group and the Hip.60' group (P < 0.05). Conclusions: Treatment with HSS was effective in preventing changes in the elastic and resistive pulmonary components, keeping them at baseline levels. Late treatment reduced perivascular and neutrophilic edema in lung tissue.
Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	80170-7
ISSN	1095-8673 ; 0022-4804
ISSN (online)	1095-8673
ISSN	0022-4804
DOI	10.1016/j.jss.2024.02.008
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Article ; Online: Can lung ultrasound predict histologic pattern of lung injury in critically ill patients with COVID-19? Author's reply.

de Almeida Monteiro, Renata Aparecida / Duarte-Neto, Amaro Nunes / Nascimento Saldiva, Paulo Hilário / Dolhnikoff, Marisa

Intensive care medicine

2021 Volume 47, Issue 5, Page(s) 631

MeSH term(s)	COVID-19 ; Critical Illness ; Humans ; Lung/diagnostic imaging ; Lung Injury/diagnostic imaging ; SARS-CoV-2
Language	English
Publishing date	2021-03-12
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	80387-x
ISSN	1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
ISSN (online)	1432-1238
ISSN	0340-0964 ; 0342-4642 ; 0935-1701
DOI	10.1007/s00134-021-06378-2
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Article ; Online: Ultrasound-Guided Minimally Invasive Autopsy of Respiratory Muscles as a Safe and Cost-Effective Technique in COVID-19 Pandemic Era.

Nucci, Ricardo Aparecido Baptista / Dolhnikoff, Marisa / Saldiva, Paulo Hilário do Nascimento / Jacob-Filho, Wilson

Acta cytologica

2021 Volume 65, Issue 3, Page(s) 276–278

MeSH term(s)	Autopsy/economics ; Autopsy/methods ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/virology ; Cost-Benefit Analysis ; Humans ; Pandemics ; Respiratory Muscles/pathology ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/physiology ; Ultrasonography/methods
Language	English
Publishing date	2021-03-09
Publishing country	Switzerland
Document type	Letter
ZDB-ID	80003-x
ISSN	1938-2650 ; 0001-5547
ISSN (online)	1938-2650
ISSN	0001-5547
DOI	10.1159/000514222
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Article: Postmortem chest computed tomography in COVID-19: A minimally invasive autopsy method.

Savoia, Paulo / Valente Yamada Sawamura, Marcio / de Almeida Monteiro, Renata Aparecida / Nunes Duarte-Neto, Amaro / Morais Martin, Maria da Graça / Dolhnikoff, Marisa / Mauad, Thais / Nascimento Saldiva, Paulo Hilário / da Costa Leite, Claudia / Ferraz da Silva, Luiz Fernando / Cardoso, Ellison Fernando

European journal of radiology open

2024 Volume 12, Page(s) 100546

Abstract: Objectives: Performing autopsies in a pandemic scenario is challenging, as the need to understand pathophysiology must be balanced with the contamination risk. A minimally invasive autopsy might be a solution. We present a model that combines radiology ... ...

Abstract	Objectives: Performing autopsies in a pandemic scenario is challenging, as the need to understand pathophysiology must be balanced with the contamination risk. A minimally invasive autopsy might be a solution. We present a model that combines radiology and pathology to evaluate postmortem CT lung findings and their correlation with histopathology. Methods: Twenty-nine patients with fatal COVID-19 underwent postmortem chest CT, and multiple lung tissue samples were collected. The chest CT scans were analyzed and quantified according to lung involvement in five categories: normal, ground-glass opacities, crazy-paving, small consolidations, and large or lobar consolidations. The lung tissue samples were examined and quantified in three categories: normal lung, exudative diffuse alveolar damage (DAD), and fibroproliferative DAD. A linear index was used to estimate the global severity of involvement by CT and histopathological analysis. Results: There was a positive correlation between patient mean CT and histopathological severity score indexes - Pearson correlation coefficient (R) = 0.66 (p = 0.0078). When analyzing the mean lung involvement percentage of each finding, positive correlations were found between the normal lung percentage between postmortem CT and histopathology (R=0.65, p = 0.0082), as well as between ground-glass opacities in postmortem CT and normal lungs in histopathology (R=0.65, p = 0.0086), but negative correlations were observed between ground-glass opacities extension and exudative diffuse alveolar damage in histological slides (R=-0.68, p = 0.005). Additionally, it was found is a trend toward a decrease in the percentage of normal lung tissue on the histological slides as the percentage of consolidations in postmortem CT scans increased (R =-0.51, p = 0.055). The analysis of the other correlations between the percentage of each finding did not show any significant correlation or correlation trends (p ≥ 0.10). Conclusions: A minimally invasive autopsy is valid. As the severity of involvement is increased in CT, more advanced disease is seen on histopathology. However, we cannot state that one specific radiological category represents a specific pathological correspondent. Ground-glass opacities, in the postmortem stage, must be interpreted with caution, as expiratory lungs may overestimate disease.
Language	English
Publishing date	2024-01-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2810314-2
ISSN	2352-0477
ISSN	2352-0477
DOI	10.1016/j.ejro.2024.100546
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Article ; Online: Using EM data to understand COVID-19 pathophysiology.

Dolhnikoff, Marisa / Duarte-Neto, Amaro N / Saldiva, Paulo H N / Caldini, Elia G

Lancet (London, England)

2020 Volume 397, Issue 10270, Page(s) 196–197

MeSH term(s)	COVID-19 ; Electrons ; Emergency Medicine ; Humans ; SARS-CoV-2
Language	English
Publishing date	2020-11-24
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(21)00034-9
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