Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages
Open accessAbstract
The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. Macrophages are a population of innate immune cells that sense and respond to microbial threats by producing inflammatory molecules that eliminate pathogens and promote tissue repair. However, a dysregulated macrophage response can be damaging to the host, as is seen in the macrophage activation syndrome induced by severe infections, including in infections with the related virus SARS-CoV. Here we describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19.
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The host appears to be the major factor explaining COVID-19 disease severity, infection rates, and long-term medical consequences.
“the host itself seems to be the major factor explaining disease severity, infection rates (Merad and Martin, 2020; Vabret et al., 2020), and long-term medical consequences (Marshall, 2020).”
From COVID-19 and the human innate immune system (2021) · cites this paper as Merad and Martin, 2020
IL-6 and TNFα can promote vascular permeability, systemic shock and multi-organ failure.
“Cytokines that mediate manifestations of ARDS, like IL-6 and TNFα, can also facilitate vascular permeability, systemic shock and multi-organ failure41,51.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [41]
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Barrett, T. J., Bilaloglu, S., Cornwell, M., Burgess, H. M., Virginio, V. W., Drenkova, K., Ibrahim, H., Yuriditsky, E., Aphinyanaphongs, Y., Lifshitz, M. S., et al. (2021) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.15534 · Cited by 203 · see citing works
Deep insight into cytokine storm: from pathogenesis to treatment
Nie, J., Zhou, L., Tian, W., Liu, X., Yang, L., Yang, X., Zhang, Y., Wei, S., Wang, D. W., & Wei, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02178-y · Cited by 224 · see citing works
- Authors
- Merad, M., & Martin, J. C.
- Affiliations
- Inserm (FR)
- Corresponding author
- Martin, Jerome C.
- ORCID
- Martin, Jerome C.
- Venue
- Nature Reviews Immunology
- Published
- 2020-05-06
- Volume
- 20
- Issue
- 6
- Pages
- 355-362
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC7201395
- OpenAlex
- W3023982717
- Cited by
- 2,472
- References
- 65
- Citations by year
- 2026: 89 · 2025: 133 · 2024: 196 · 2023: 330 · 2022: 529 · 2021: 753 · 2020: 435 · 2019: 2 · 2018: 3
- FWCI
- 24.29
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-06-02)
- Open access
- bronze
- doi.org
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Icahn School of Medicine at Mount Sinai
- Agence Nationale de la Recherche (ANR-16-IDEX-0007)
- Institut National de la Santé et de la Recherche Médicale
- Université de Nantes
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- COVID-19 pandemic, SARS-CoV-2, monocytes, macrophages, hyperinflammation, macrophage activation syndrome, innate immunity, inflammatory signaling
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Animals, Humans, Inflammation, Macrophage Activation, Macrophages, Monocytes, Pneumonia, Viral, Coronavirus Infections, Pandemics
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