A new study has suggested that the antiviral response of the body to the initial infection when the virus enters the nose, affects the severity of Covid-19.

Researchers analysed 58 frozen nasopharyngeal swabs collected from Covid-19 patients at the time of the initial diagnosis and healthy controls. High quality single-cell RNA sequencing (scRNA-seq) of swabs was done and patients who developed mild disease were compared with those who progressed to more severe disease and required to be intubated in due course of time.

Single-cell RNA-seq profiling highlights novel rare cell states of the repairing airway epithelium¹

Analysis of samples showed a significant loss of mature ciliated cells following SARS-CoV-2 infection. These ciliated cells are associated with secretory cell expansion, differentiation and accumulation of deuterosomal cell intermediates in the process of regeneration of the damaged epithelium. The deuterosomal cells are intermediate between secretory and multiciliated cells.¹

Epithelial cells in patients with mild to moderate Covid-19 were observed to express anti-viral/interferon-responsive genes, whereas the IFN response was markedly blunted in patients who progressed to severe disease. An increase in the number of interferon responsive ciliated cells, 15.9% of all epithelial cells, were found in patients with mild to moderate Covid-19 compared to < 1% among healthy controls.

Patients with severe Covid-19 also showed mucosal recruitment of highly inflammatory myeloid cells, which are the primary sources of tissue pro-inflammatory cytokines (TNF, IL1B, CXCL8).

A decrease in the number of cilia ^high and BEST4^highcilia^high ciliated cells (ciliated cell subtypes) was observed in Covid-19 patients, particularly in patients with severe disease. This reduction in number may be due to delayed replenishment from secretory or deuterosomal precursors or increased susceptibility to viral-mediated pathogenesis. The study findings are published in the journal Cell.²

The nose and the mouth act as a portal of entry for the SARS-CoV-2. The virus initially replicates in the nasopharynx in the infected persons, even in asymptomatic individuals, who become potential sources of infection. Viral replication manifests clinically as an upper respiratory infection. Some patients develop lower respiratory infection where a combination of inflammatory immune responses and direct viral mediated pathogenesis can lead to diffuse damage to distal airways, alveoli and vasculature.

This study has shown that SARS-CoV-2 infection leads to changes in the composition of the respiratory epithelium. Also, in patients with severe Covid-19, the impairment of intrinsic anti-viral immunity to SARS-CoV-2 infection in the nasal epithelial cells permits the virus to replicate and spread from upper to lower respiratory tract. Increased recruitment of the inflammatory cells contributes to the hyperinflammatory response and progression to severe disease.

References

1. J Cyst Fibros. 2020;19 Suppl 1:S42-S46
2. Ziegler CG, et al. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe Covid-19. Cell. 2021. https://doi.org/10.1016/j.cell.2021.01.023.

 Dr Surya Kant,

Professor and Head, Dept. of Respiratory Medicine, KGMU, UP, Lucknow.

National Vice Chairman IMA-AMS