journal article·2022-12-01

Ultracellular Imaging of Bronchoalveolar Lavage from Young COVID-19 Patients with Comorbidities Showed Greater SARS-COV-2 Infection but Lesser Ultrastructural Damage Than the Older Patients

Shikha Chaudhary, Preeti Rai, Arti Joshi, Pooja Yadav, Kishore Sesham, Shailendra Kumar, Asit Ranjan Mridha, Upendra Baitha, Tapas Chandra Nag, Kapil Dev Soni, Anjan Trikha, Subhash Chandra Yadav

Microscopy and Microanalysis· Volume 28· Issue 6
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Abstract

Abstract In this study, we examined the cellular infectivity and ultrastructural changes due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the various cells of bronchoalveolar fluid (BALF) from intubated patients of different age groups (≥60 years and <60 years) and with common comorbidities such as diabetes, liver and kidney diseases, and malignancies. BALF of 79 patients (38 cases >60 and 41 cases <60 years) were studied by light microscopy, immunofluorescence, scanning, and transmission electron microscopy to evaluate the ultrastructural changes in the ciliated epithelium, type II pneumocytes, macrophages, neutrophils, eosinophils, lymphocytes, and anucleated granulocytes. This study demonstrated relatively a greater infection and better preservation of subcellular structures in these cells from BALF of younger patients (<60 years compared with the older patients (≥60 years). The different cells of BALF from the patients without comorbidities showed higher viral load compared with the patients with comorbidities. Diabetic patients showed maximum ultrastructural damage in BALF cells in the comorbid group. This study highlights the comparative effect of SARS-CoV-2 infection on the different airway and inflammatory cells of BALF at the subcellular levels among older and younger patients and in patients with comorbid conditions.
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Research context

OpenAlex topics: Respiratory Support and Mechanisms · Respiratory viral infections research · COVID-19 Clinical Research Studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

All India Institute of Medical Sciences Electron Microscope Facility, Department of Anatomy, , New Delhi, Delhi 110029, India

All India Institute of Medical Sciences Department of Pathology, , New Delhi, Delhi 110029, India

All India Institute of Medical Sciences Department of Anaesthesiology, Pain Medicine and Critical Care, , New Delhi, Delhi 110029, India

All India Institute of Medical Sciences Department of Medicine, , New Delhi, Delhi 110029, India

All India Institute of Medical Sciences Anaesthesia and Critical Care, JPN Apex Trauma Center, , New Delhi, Delhi 110029, India

Funding

IUSSTF Indo-US Virtual Network for the COVID-19 program

References (92)

Show source-provided references
1. Update on the pathogenesis of chronic obstructive pulmonary disease10.1056/NEJMra1900475 ↗
2. Nasal ciliated cells are primary targets for SARS-CoV-2 replication in the early stage of COVID-1910.1172/JCI148517 ↗
3. Understanding the molecular biology of SARS-CoV-2 and the COVID-19 pandemic: A review10.2147/IDR.S306441 ↗
4. The proximal origin of SARS-CoV-210.1038/s41591-020-0820-9 ↗
5. Aging, immunity, and COVID-19: How age influences the host immune response to coronavirus infections?10.3389/fphys.2020.571416 ↗
6. Neutrophil extracellular traps kill bacteria10.1126/science.1092385 ↗
7. Nasal gene expression of angiotensin-converting enzyme 2 in children and adults10.1001/jama.2020.8707 ↗
8. The fibroproliferative response in acute respiratory distress syndrome: Mechanisms and clinical significance10.1183/09031936.00196412 ↗
9. Microscopic imaging of bronchoalveolar fluids of COVID-19 positive intubated patients reveals the different level of SARS-CoV-2 infection on oral squamosal epithelial cells
10. Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation10.1111/acel.13168 ↗
11. Macrophage polarization and its role in the pathogenesis of acute lung injury/acute respiratory distress syndrome10.1007/s00011-020-01378-2 ↗
12. COVID-19 Infection and circulating ACE2 levels: Protective role in women and children10.3389/fped.2020.00206 ↗
13. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1alpha/glycolysis-dependent axis10.1016/j.cmet.2020.07.007 ↗
14. Fatal eosinophilic myocarditis in a healthy 17-year-old male with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2c)10.1080/15513815.2020.1761491 ↗
15. Three-dimensional cell cultures as a research platform in lung diseases and COVID-1910.1007/s13770-021-00348-x ↗
16. The intriguing ultrastructure of lipid body organelles within activated macrophages10.1017/S143192761400066X ↗
17. Clinical features of 85 fatal cases of COVID-19 from Wuhan. A retrospective observational study10.1164/rccm.202003-0543OC ↗
18. Organoids of human airways to study infectivity and cytopathy of SARS-CoV-210.1016/S2213-2600(20)30238-1 ↗
19. Q&A: The novel coronavirus outbreak causing COVID-1910.1186/s12916-020-01533-w ↗
20. Lung remodeling associated with recovery from acute lung injury10.1007/s00441-016-2521-8 ↗
21. Clinical characteristics of coronavirus disease 2019 in China10.1056/NEJMoa2002032 ↗
22. Anti-vascular endothelial growth factor gene therapy attenuates lung injury and fibrosis in mice10.4049/jimmunol.175.2.1224 ↗
23. Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction10.1152/ajplung.00232.2013 ↗
24. SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract10.1016/j.cell.2020.05.042 ↗
25. Characteristics of SARS-CoV-2 and COVID-1910.1038/s41579-020-00459-7 ↗
26. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China10.1016/S0140-6736(20)30183-5 ↗
27. SARS-CoV-2 infection of the oral cavity and saliva10.1038/s41591-021-01296-8 ↗
28. Pulmonary macrophage subpopulations in the induction and resolution of acute lung injury10.1165/rcmb.2012-0090OC ↗
29. Association of obesity with disease severity among patients with coronavirus disease 201910.1002/oby.22859 ↗
30. Enhanced eosinophil-mediated inflammation associated with antibody and complement-dependent pneumonic insults in critical COVID-1910.1016/j.celrep.2021.109798 ↗
31. The role of macrophages in the pathogenesis of SARS-CoV-2-associated acute respiratory distress syndrome10.3389/fimmu.2021.682871 ↗
32. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges10.1016/j.ijantimicag.2020.105924 ↗
33. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: Estimation and application10.7326/M20-0504 ↗
34. Eosinophilic panniculitis associated with COVID-1910.1016/j.ad.2020.05.003 ↗
35. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia10.1056/NEJMoa2001316 ↗
36. Acute respiratory failure in COVID-19: Is it “typical” ARDS?10.1186/s13054-020-02911-9 ↗
37. Eosinophil responses during COVID-19 infections and coronavirus vaccination10.1016/j.jaci.2020.04.021 ↗
38. SARS-CoV-2 cell tropism and multiorgan infection10.1038/s41421-021-00249-2 ↗
39. On the dependency of cellular protein levels on mRNA abundance10.1016/j.cell.2016.03.014 ↗
40. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding10.1016/S0140-6736(20)30251-8 ↗
41. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases10.1016/j.trsl.2020.04.007 ↗
42. Pathology and pathogenesis of SARS-CoV-2 associated with fatal coronavirus disease, United States10.3201/eid2609.202095 ↗
43. Acute respiratory distress syndrome10.7861/clinmedicine.16-6-s66 ↗
44. Thoughts on the alveolar phase of COVID-1910.1152/ajplung.00126.2020 ↗
45. Acute lung injury and the acute respiratory distress syndrome: Pathophysiology and treatment
46. COVID-19: Consider cytokine storm syndromes and immunosuppression10.1016/S0140-6736(20)30628-0 ↗
47. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome10.1182/blood.2020007008 ↗
48. Macrophage activation syndrome and COVID-1910.1186/s41232-020-00131-w ↗
49. Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): A study of 63 patients in Wuhan, China10.1007/s00330-020-06731-x ↗
50. Effects of mechanical ventilation on the extracellular matrix10.1007/s00134-007-0964-9 ↗
51. Should COVID-19 concern nephrologists? Why and to what extent? The emerging impasse of angiotensin blockade10.1159/000507305 ↗
52. Immunopathogenesis of coronavirus infections: Implications for SARS10.1038/nri1732 ↗
53. Intracellular origin and ultrastructure of platelet-derived microparticles10.1111/jth.13745 ↗
54. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized With COVID-19 in the New York city area10.1001/jama.2020.6775 ↗
55. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak10.1016/j.jaut.2020.102433 ↗
56. Direct evidence of secondary necrosis of neutrophils during intense lung inflammation10.1183/09031936.06.00126905 ↗
57. Progenitor identification and SARS-CoV-2 infection in human distal lung organoids10.1038/s41586-020-3014-1 ↗
58. Comorbidity and its impact on patients with COVID-1910.1007/s42399-020-00363-4 ↗
59. Risk factors for poor prognosis in children and adolescents with COVID-19: A systematic review and meta-analysis10.1016/j.eclinm.2021.101155 ↗
60. Neutrophil diversity in health and disease10.1016/j.it.2019.04.012 ↗
61. A single-cell RNA expression map of human coronavirus entry factors10.1016/j.celrep.2020.108175 ↗
62. Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis10.1172/JCI141374 ↗
63. Respiratory drive in the acute respiratory distress syndrome: Pathophysiology, monitoring, and therapeutic interventions10.1007/s00134-020-05942-6 ↗
64. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes10.1038/s41591-020-0868-6 ↗
65. Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: Analysis of underlying signal transduction pathways and potential diagnostic utility10.1186/ar4579 ↗
66. Roles of oxidants and redox signaling in the pathogenesis of acute respiratory distress syndrome10.1089/ars.2007.1940 ↗
67. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies10.1038/s41379-020-0536-x ↗
68. Injurious ventilation induces widespread pulmonary epithelial expression of tumor necrosis factor-alpha and interleukin-6 messenger RNA10.1097/00003246-200208000-00003 ↗
69. Differential alveolar epithelial injury and protein expression in pneumococcal pneumonia10.3109/01902148.2012.683321 ↗
70. SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology10.1084/jem.20201129 ↗
71. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection10.1016/j.ejim.2020.04.037 ↗
72. Coronavirus biology and replication: Implications for SARS-CoV-210.1038/s41579-020-00468-6 ↗
73. Roles and origins of leukocyte lipid bodies: Proteomic and ultrastructural studies10.1096/fj.06-6711com ↗
74. Clinical characteristics of 138 hospitalized patients With 2019 novel coronavirus-infected pneumonia in Wuhan, China10.1001/jama.2020.1585 ↗
75. The role of pulmonary surfactants in the treatment of acute respiratory distress syndrome in COVID-1910.3389/fphar.2021.698905 ↗
76. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China10.1002/jmv.25689 ↗
77. Detection of SARS-associated coronavirus in throat wash and saliva in early diagnosis10.3201/eid1007.031113 ↗
78. Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages10.1038/s41422-020-00455-9 ↗
79. Functions of tissue-resident eosinophils10.1038/nri.2017.95 ↗
80. Acute lung injury and the acute respiratory distress syndrome: A clinical review10.1016/S0140-6736(07)60604-7 ↗
81. Factors associated with COVID-19-related death using OpenSAFELY10.1038/s41586-020-2521-4 ↗
82. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing10.1038/nm.3887 ↗
83. Wood · 2020
84. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China10.1001/jamainternmed.2020.0994 ↗
85. Pathological findings of COVID-19 associated with acute respiratory distress syndrome10.1016/S2213-2600(20)30076-X ↗
86. COVID-19 mortality risk for older men and women10.1186/s12889-020-09826-8 ↗
87. Ultra- and micro-structural changes of respiratory tracts in SARS-CoV-2 infected Syrian hamsters10.1186/s13567-021-00988-w ↗
88. The immune system and COVID-19: Friend or foe?10.1016/j.lfs.2020.117900 ↗
89. ACE2: Evidence of role as entry receptor for SARS-CoV-2 and implications in comorbidities10.7554/eLife.61390 ↗
90. Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy10.1038/s41392-021-00653-w ↗
91. Cell morphological analysis of SARS-CoV-2 infection by transmission electron microscopy10.21037/jtd-20-1368 ↗
92. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study10.1016/S0140-6736(20)30566-3 ↗