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.

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.

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.

Downregulation of the host cell pro-apoptotic pathways confers a selective advantage to viral pathogens, and many viruses interfere with such regulatory mechanisms in order to enhance their propagation in infected cells. The Scribble cell polarity complex, which is composed of multiple adapter proteins including human Scribble, Dlg and MAGI, controls a variety of host cell functionalities including apoptosis, morphology, polarity, signaling and migration. In the recent years, components from several viral pathogens, including oncogenic viruses, have been found to associate with and modulate the activities of this complex, particularly that of the pro-apoptotic protein Scribble. Here, we establish a critical role for the downregulation of Scribble expression for the potentiation of Chikungunya Virus (CHIKV) infection. CHIKV is a well-known mosquito-borne alphavirus, which has caused outbreaks in more than 100 countries and constitutes a global health hazard. While the majority of the CHIKV proteome is well characterized, the role of a small structural protein 6K, and its transframe variant, TF, which is generated from the 6K sequence by ribosomal slippage and frameshifting, is not established as yet. We show that TF triggers the punctation, ubiquitination and degradation of Scribble during CHIKV infection, and that the downregulation of Scribble during CHIKV infection. We show that the association of TF with the PDZ domains of Scribble is mediated through a PDZ-domain binding motif at the C-terminus of TF. Thus, our work establishes a role for the downregulation of Scribble in alphavirus infections for the first time, while allocating a novel role in host modulation to the mysterious 6K/TF component of alphaviruses.