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

Abstract

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.

A Nanobody Interaction with SARS-CoV-2 Spike Allows the Versatile Targeting of Lentivirus Vectors

“…Our results are consistent with observations that SARS-CoV-2-infected cells form syncytia, indicative of activated Spike proteins on infected cell surfaces (11–18). Our results also demonstrate that perturbations of host cell functions by SARS-CoV-2 infection are not sufficient to prevent lentivirus vector delivery and expression (19–21).…”

Infection kinetics, syncytia formation, and inflammatory biomarkers as predictive indicators for the pathogenicity of SARS-CoV-2 Variants of Concern in Calu-3 cells

“…Post-mortem lung tissues obtained from COVID-19 patients who died also revealed the formation of syncytia in fused pneumocytes, indicating productive infection. These studies confirmed the presence of large multinucleated pneumocytes as a significant feature of severe lung damage [ 24 , 63 ]. Syncytia with more nuclei or those that are larger in size are more likely to internalize lymphocytes [ 60 ].…”

Age-specific nasal epithelial responses to SARS-CoV-2 infection

“…Such functional changes facilitate disease progression and potentially enhance viral spread 45 , 46 . Ultrastructural and immunofluorescence studies confirm significant SARS-CoV-2 infection in shed cells in severe COVID-19 cases 47 . Elevated vimentin levels, an EMT and basaloid cell marker, are also present in these cultures.…”