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

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

doi:10.1017/s1431927622012430

Cited by 3 publications

(1 citation statement)

References 96 publications

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“…Multiple anucleate cells or their fragments with a very high level of infection in severe ARDS patients with and without HCQ indicate the negligible impact of HCQs in these cells. These cells have identified a granulocyte due to CD 15 positive in the immunohistochemistry 47 . The phagocytic vesicles were filled with mature viruses indicating that HCQs may increase the phagocytic activity of granulocytes (Fig.…”

Section: Discussionmentioning

confidence: 96%

Impact of prophylactic hydroxychloroquine on ultrastructural impairment and cellular SARS-CoV-2 infection in different cells of bronchoalveolar lavage fluids of COVID-19 patients

Chaudhary,

Joshi,

Sesham

et al. 2023

Sci Rep

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Many drugs were recommended as antiviral agents for infection control and effective therapy to reduce the mortality rate for COVID-19 patients. Hydroxychloroquine (HCQ), an antimalarial drug, has been controversially recommended for prophylactic use in many countries, including India, to control SARS-CoV-2 infections. We have explored the effect of prophylactic HCQ from the cells of bronchoalveolar lavage fluids from COVID-19-induced acute respiratory distress syndrome patients to determine the level of infection and ultrastructural alterations in the ciliated epithelium, type II pneumocytes, alveolar macrophages, neutrophils, and enucleated granulocytes. Ultrastructural investigation of ciliated epithelium and type II pneumocytes showed lesser infections and cellular impairment in the prophylactic HCQ+ group than HCQ− group. However, macrophages and neutrophils displayed similar infection and ultrastructural alterations in both patient groups. The enucleated fragments of granulocytes showed phagocytosis of the matured virus in HCQ+ groups. The present report unveils the ultrastructural proof to complement the paradox regarding the role of prophylactic HCQ in COVID-19 patients.

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Section: Discussionmentioning

confidence: 96%

Impact of prophylactic hydroxychloroquine on ultrastructural impairment and cellular SARS-CoV-2 infection in different cells of bronchoalveolar lavage fluids of COVID-19 patients

Chaudhary,

Joshi,

Sesham

et al. 2023

Sci Rep

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Ultrastructural study confirms the formation of single and heterotypic syncytial cells in bronchoalveolar fluids of COVID-19 patients

Chaudhary

Yadav

Kumar

et al. 2023

Virol J

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Background SARS-CoV-2 was reported to induce cell fusions to form multinuclear syncytia that might facilitate viral replication, dissemination, immune evasion, and inflammatory responses. In this study, we have reported the types of cells involved in syncytia formation at different stages of COVID-19 disease through electron microscopy. Methods Bronchoalveolar fluids from the mild (n = 8, SpO2 > 95%, no hypoxia, within 2–8 days of infection), moderate (n = 8, SpO2 90% to ≤ 93% on room air, respiratory rate ≥ 24/min, breathlessness, within 9–16 days of infection), and severe (n = 8, SpO2 < 90%, respiratory rate > 30/min, external oxygen support, after 17th days of infection) COVID-19 patients were examined by PAP (cell type identification), immunofluorescence (for the level of viral infection), scanning (SEM), and transmission (TEM) electron microscopy to identify the syncytia. Results Immunofluorescence studies (S protein-specific antibodies) from each syncytium indicate a very high infection level. We could not find any syncytial cells in mildly infected patients. However, identical (neutrophils or type 2 pneumocytes) and heterotypic (neutrophils-monocytes) plasma membrane initial fusion (indicating initiation of fusion) was observed under TEM in moderately infected patients. Fully matured large-size (20–100 μm) syncytial cells were found in severe acute respiratory distress syndrome (ARDS-like) patients of neutrophils, monocytes, and macrophage origin under SEM. Conclusions This ultrastructural study on the syncytial cells from COVID-19 patients sheds light on the disease’s stages and types of cells involved in the syncytia formations. Syncytia formation was first induced in type II pneumocytes by homotypic fusion and later with haematopoetic cells (monocyte and neutrophils) by heterotypic fusion in the moderate stage (9–16 days) of the disease. Matured syncytia were reported in the late phase of the disease and formed large giant cells of 20 to 100 μm.

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Ultrastructural study confirms the formation of single and heterotypic syncytial cells in bronchoalveolar fluids of COVID-19 patients

Chaudhary

Yadav

Kumar

et al. 2022

Preprint

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Background SARS-CoV-2 was reported to induce cell fusions to form multinuclear syncytia that might facilitate viral replication, dissemination, immune evasion, and inflammatory responses. In this study, we have reported the types of cells involved in syncytia formation at different stages of COVID-19 disease through electron microscopy. Methods Bronchoalveolar fluids from the mild (n = 8, 2–8 days), moderate (n = 8, 9–16 days), and severe (n = 8, after 17th days) COVID-19 patients were examined by PAP (cell type identification), immunofluorescence (for the level of viral infection), scanning (SEM), and transmission (TEM) electron microscopy to identify the syncytia. Results Immunofluorescence studies (S protein-specific antibodies) from each syncytium cell indicate a very high infection level. We could not find any syncytial cells in mildly infected patients. However, identical (neutrophils or type 2 pneumocytes) and heterotypic (neutrophils-monocytes) plasma membrane initial fusion (indicating initiation of fusion) was observed under TEM in moderately infected patients. Fully matured large-size (20–100µm) syncytial cells were found in severe ARDS patients of neutrophils, monocytes, and macrophage origin under SEM. Conclusions This ultrastructural study on the syncytial cells from COVID-19 patients sheds light on the disease's stages and types of cells involved in the syncytia formations. Syncytia formation was first induced in type II pneumocytes by homotypic fusion and later with haematopoetic cells (monocyte and neutrophils) by heterotypic fusion in the moderate stage (9–16 days) of the disease. Matured syncytia were reported in the late phase of the disease and formed large giant cells of 40 to 100 µm.

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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

Cited by 3 publications

References 96 publications

Impact of prophylactic hydroxychloroquine on ultrastructural impairment and cellular SARS-CoV-2 infection in different cells of bronchoalveolar lavage fluids of COVID-19 patients

Impact of prophylactic hydroxychloroquine on ultrastructural impairment and cellular SARS-CoV-2 infection in different cells of bronchoalveolar lavage fluids of COVID-19 patients

Ultrastructural study confirms the formation of single and heterotypic syncytial cells in bronchoalveolar fluids of COVID-19 patients

Ultrastructural study confirms the formation of single and heterotypic syncytial cells in bronchoalveolar fluids of COVID-19 patients

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