COVID-19: imbalanced cell-mediated immune response drives to immunopathology

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an imminent threat to humanity. SARS-CoV-2 invades host cells, causing a failure of host immune recognition. Instead of an effective antiviral immunological response after SARS-CoV-2 invasion, the cascading pathological syndrome of COVID-19, especially in severe disease, is exacerbated by an overt inflammatory response and the suppression of SARS-CoV-2–specific immune responses. As is known, excessive inflammation leads to pathophysiological changes in virus-infected tissues or organs, manifested by imbalanced immune responses, cytokine storm, and aggressive neutrophil activation, ultimately leading to lung damage, such as alveolar damage, endotheliitis, and fluid overload. However, the triggers and consequences of a disruption to immune system homeostasis and the underlying mechanisms of uncontrolled immunopathology following viral infection remain unclear. Here, we review the dynamic and systemic immune progression from an imbalance in cell-mediated immune responses to COVID-19 lung injury. Our understanding of key mechanisms involved in pathogenesis is critical for the development of therapeutic agents and to optimize therapeutic strategies.

KEYWORDS:

• COVID-19
• SARS-CoV-2
• NETs
• pathogenesis
• cytokine storm

Acknowledgements

The authors are grateful for all supplied grants. We thank Prof. Hongzhou Lu and Prof. Yuanwang Qiu for excellent guidance. We thank the letpub company for language correction of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Science Foundation of China (grant numbers 82072281, 81971915); Basic and Applied Basic Research Fund of Guangdong Province: Regional Joint Fund-Youth Fund Project (grant number 2020A15151108031), a grant from the Guangdong Provincial Department of Science and Technology; Chinese Post-doctoral Science Foundation (grant number 2022M711486), a grant from China Post-doctor's office; The Top Talent Support Program for young and middle-aged people from Wuxi Health Committee (grant number BJ2020091).