Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 1;321(2):L485-L489.
doi: 10.1152/ajplung.00231.2021. Epub 2021 Jul 7.

Erythrocytes identify complement activation in patients with COVID-19

L K Metthew Lam  1   2 , John P Reilly  1   2 , Ann H Rux  3 , Sophia J Murphy  1 , Leticia Kuri-Cervantes  4   5 , Ariel R Weisman  1 , Caroline A G Ittner  1 , M Betina Pampena  4   5 , Michael R Betts  4   5 , E John Wherry  5   6   7 , Wen-Chao Song  5   6 , John D Lambris  3 , Nuala J Meyer  1   2   5   8 , Douglas B Cines  2   3   5 , Nilam S Mangalmurti  1   2   5   8
Affiliations

Erythrocytes identify complement activation in patients with COVID-19

L K Metthew Lam et al. Am J Physiol Lung Cell Mol Physiol. .

Abstract

COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized by respiratory failure, arrhythmias, thromboembolic complications, and shock with high mortality. Autopsy and preclinical evidence implicate aberrant complement activation in endothelial injury and organ failure. Erythrocytes express complement receptors and are capable of binding immune complexes; therefore, we investigated complement activation in patients with COVID-19 using erythrocytes as a tool to diagnose complement activation. We discovered enhanced C3b and C4d deposition on erythrocytes in COVID-19 sepsis patients and non-COVID sepsis patients compared with healthy controls, supporting the role of complement in sepsis-associated organ injury. Our data suggest that erythrocytes may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis and identifying patients who may benefit from complement targeted therapies.

Keywords: COVID-19; SARS-CoV-2; complement; erythrocyte; sepsis.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Complement activation and deposition on RBCs during COVID-sepsis and non-COVID sepsis. A: ELISA for C3/C3b/iC3b deposition on immobilized spike protein. Plasma from healthy donors and patients with COVID-19 was tested, n = 4–9 subjects, P < 0.004. B: C3 deposition on RBCs from healthy donors (HD, n = 10), patients hospitalized with COVID-19-associated organ injury (n = 72), and COVID-negative septic patients (n = 11) evaluated on day (d) 0 of ICU admission (P = 0.0025 and P = 0.0021, one-way ANOVA with Dunn’s post hoc; HD vs. COVID and HD vs. non-COVID sepsis). C: C3 and CoV spike protein detection on RBCs, bright green punctae indicate positive staining, RBCs from a healthy donor are shown for control. Results were quantified and correlations between d0 and d7 are shown in D, d0: r2 = 0.59, P = 0.01; d7: r2 = 0.78, P = 0.014. E: C3 deposition on RBCs in patients with COVID. Comparison of C3 on RBCs at d0 and d7 of study enrollment, P = 0.0017, t test. F: RBC-bound C3 from individual patients on d0 and d7, P = 0.0069, paired t test. G: C4d deposition on RBCs from patients with COVID-19 (one-way ANOVA, Dunn’s post hoc). CoV-S, coronavirus-spike protein; ICU, intensive care unit; OD, optical density; RBCs, red blood cells.
See this image and copyright information in PMC

Update of

References

    1. Anesi GL, Jablonski J, Harhay MO, Atkins JH, Bajaj J, Baston C, et al. Characteristics, outcomes, and trends of patients with COVID-19-related critical illness at a learning health system in the United States. Ann Intern Med 174: 613–621, 2021. doi: 10.7326/M20-5327. - DOI - PMC - PubMed
    1. Liu Y, Yan L-M, Wan L, Xiang T-X, Le A, Liu J-M, Peiris M, Poon LLM, Zhang W. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 20: 656–657, 2020. doi: 10.1016/S1473-3099(20)30232-2. - DOI - PMC - PubMed
    1. Holter JC, Pischke SE, de Boer E, Lind A, Jenum S, Holten AR, Tonby K, Barratt-Due A, Sokolova M, Schjalm C, Chaban V, Kolderup A, Tran T, Gjolberg TT, Skeie LG, Hesstvedt L, Ormasen V, Fevang B, Austad C, Muller KE, Fladeby C, Holberg-Petersen M, Halvorsen B, Muller F, Aukrust P, Dudman S, Ueland T, Andersen JT, Lund-Johansen F, Heggelund L, Dyrhol-Riise AM, Mollnes TE. Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients. Proc Natl Acad Sci USA 117: 25018–25025, 2020. doi: 10.1073/pnas.2010540117. - DOI - PMC - PubMed
    1. Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res 220: 1–13, 2020. doi: 10.1016/j.trsl.2020.04.007. - DOI - PMC - PubMed
    1. Gao T, Hu M, Zhang X, Li H, Zhu L, Liu H, et al. Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation (Preprint). medRxiv, 2020. doi: 10.1101/2020.03.29.20041962. - DOI

Publication types

MeSH terms