RESUMO
Background: COVID-19 lung sequelae can impact the course of patient lives. We investigated the evolution of pulmonary abnormalities in post-COVID-19 patients 18-24 months after hospital discharge. Methods: A cohort of COVID-19 patients admitted to the Hospital das Clínicas da Faculdade de Medicina da USP in São Paulo, Brazil, between March and August of 2020, were followed-up 6-12 months after hospital discharge. A subset of patients with pulmonary involvement and chest computed tomography (CT) scans were eligible to participate in this second follow-up (18-24 months). Data was analyzed in an ambidirectional manner, including retrospective data from the hospitalization, and from the first follow-up (6-12 months after discharge), and compared with the prospective data collected in this new follow-up. Findings: From 348 patients eligible, 237 (68%) participated in this follow-up. Among participants, 139 (58%) patients presented ground-glass opacities and reticulations, and 80 (33%) presented fibrotic-like lesions (traction bronchiectasis and architectural distortion). Five (2%) patients improved compared to the 6-12-month assessment, but 20 (25%) of 80 presented worsening of lung abnormalities. For those with relevant assessments on both occasions, comparing the CT findings between this follow-up with the previous assessment, there was an increase in patients with architectural distortion (43 [21%] of 204 vs 57 [28%] of 204, p = 0.0093), as well as in traction bronchiectasis (55 [27%] of 204 vs 69 [34%] of 204, p = 0.0043). Patients presented a persistent functional impairment with demonstrated restrictive pattern in both follow-ups (87 [42%] of 207 vs 91 [44%] of 207, p = 0.76), as well as for the reduced diffusion capacity (88 [42%] of 208 vs 87 [42%] of 208, p = 1.0). Length of hospitalization (OR 1.04 [1.01-1.07], p = 0.0040), invasive mechanical ventilation (OR 3.11 [1.3-7.5] p = 0.011), patient's age (OR 1.03 [1.01-1.06] p = 0.0074 were consistent predictors for development of fibrotic-like lung lesions in post-COVID-19 patients. Interpretation: Post-COVID-19 lung sequelae can persist and progress after hospital discharge, suggesting airways involvement and formation of new fibrotic-like lesions, mainly in patients who were in intensive care unit (ICU). Funding: São Paulo Research Foundation (22/01769-5) and Instituto Todos pela Saúde (C1721).
RESUMO
Boron nitride (BN) nanomaterials have drawn a lot of interest in the material science community. However, extensive research is still needed to thoroughly analyze their safety profiles. Herein, we investigated the pulmonary impact and clearance of two-dimensional hexagonal boron nitride (h-BN) nanosheets and boron nitride nanotubes (BNNTs) in mice. Animals were exposed by single oropharyngeal aspiration to h-BN or BNNTs. On days 1, 7, and 28, bronchoalveolar lavage (BAL) fluids and lungs were collected. On one hand, adverse effects on lungs were evaluated using various approaches (e.g., immune response, histopathology, tissue remodeling, and genotoxicity). On the other hand, material deposition and clearance from the lungs were assessed. Two-dimensional h-BN did not cause any significant immune response or lung damage, although the presence of materials was confirmed by Raman spectroscopy. In addition, the low aspect ratio h-BN nanosheets were internalized rapidly by phagocytic cells present in alveoli, resulting in efficient clearance from the lungs. In contrast, high aspect ratio BNNTs caused a strong and long-lasting inflammatory response, characterized by sustained inflammation up to 28 days after exposure and the activation of both innate and adaptive immunity. Moreover, the presence of granulomatous structures and an indication of ongoing fibrosis as well as DNA damage in the lung parenchyma were evidenced with these materials. Concurrently, BNNTs were identified in lung sections for up to 28 days, suggesting long-term biopersistence, as previously demonstrated for other high aspect ratio nanomaterials with poor lung clearance such as multiwalled carbon nanotubes (MWCNTs). Overall, we reveal the safer toxicological profile of BN-based two-dimensional nanosheets in comparison to their nanotube counterparts. We also report strong similarities between BNNTs and MWCNTs in lung response, emphasizing their high aspect ratio as a major driver of their toxicity.