Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Understanding of the fundamental processes underlying the versatile clinical manifestations of COVID-19 is incomplete without comprehension of how different immune cells are recruited to various compartments of virus-infected lungs, and how this recruitment differs among individuals with different levels of disease severity. As in other respiratory infections, leukocyte recruitment to the respiratory system in people with COVID-19 is orchestrated by specific leukocyte trafficking molecules, and when uncontrolled and excessive it results in various pathological complications, both in the lungs and in other organs. In the absence of experimental data from physiologically relevant animal models, our knowledge of the trafficking signals displayed by distinct vascular beds and epithelial cell layers in response to infection by SARS-CoV-2 is still incomplete. However, SARS-CoV-2 and influenza virus elicit partially conserved inflammatory responses in the different respiratory epithelial cells encountered early in infection and may trigger partially overlapping combinations of trafficking signals in nearby blood vessels. Here, we review the molecular signals orchestrating leukocyte trafficking to airway and lung compartments during primary pneumotropic influenza virus infections and discuss potential similarities to distinct courses of primary SARS-CoV-2 infections. We also discuss how an imbalance in vascular activation by leukocytes outside the airways and lungs may contribute to extrapulmonary inflammatory complications in subsets of patients with COVID-19. These multiple molecular pathways are potential targets for therapeutic interventions in patients with severe COVID-19.
| Original language | English |
|---|---|
| Pages (from-to) | 49-64 |
| Number of pages | 16 |
| Journal | Nature Reviews Immunology |
| Volume | 21 |
| Issue number | 1 |
| Early online date | 19 Nov 2020 |
| DOIs | |
| Publication status | Published - Jan 2021 |
Funding
The authors thank S. Jung, I. Sagi and S. Feigelson (Weizmann Institute of Science), A. Sapoznikov (Israel Institute for Biological Research, Ness-Ziona), A. Rot (Queen Mary University of London, UK) and A. Ariel (University of Haifa, Israel) for fruitful discussions. They also thank S. Schwarzbaum for editorial assistance. This work was supported by GIF I-1470-412.13/2018, ISF 791/17, funds from the Minerva Foundation, ERA-Net E-Rate-3, and the Ministry of Health of Israel (to R.A.). This project was also funded in part by federal funds from the US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under CEIRS contract no. HHSN272201400005C (to D.J.T.) and P01-AI102851 (to D.J.T., D. Fowell, principal investigator) as well as 1U01HL122700 (to G. Pryhuber of the LungMAP Biorepository at the University of Rochester) and training grant GM007356 to M.S. N.G.’s research is supported by the BMBF (COVIMMUNE consortium) and the German Research Foundation grants EXC 2151, 390873048, 369799452 and 272482170. A.Z.’s research is supported by German Research Foundation grants ZA428/12-1, SFB1009A05 ZA428/18-1 and ZA428/17-1 and by IZKF grant Za2/001/18. Author contributions - R.A. wrote the leukocyte trafficking sections of this Perspective and coordinated the writing of other sections and boxes. D.J.T., N.G. and A.Z. wrote specific sections and revised the Perspective. D.J.T. and R.A. supervised the writing of paragraphs contributed by M.S., S.K., A.K. and E.C.R.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology