Neutrophil Extracellular Traps Contribute to COVID-19 Hyperinflammation and Humoral Autoimmunity.
Torres-Ruiz. Jiram J; Absalón-Aguilar. Abdiel A; Nuñez-Aguirre. Miroslava M; Pérez-Fragoso. Alfredo A; Carrillo-Vázquez. Daniel Alberto DA; Maravillas-Montero. José Luis JL; Mejía-Domínguez. Nancy R NR; Llorente. Luis L; Alcalá-Carmona. Beatriz B; Lira-Luna. Jaquelin J; Núñez-Álvarez. Carlos C; Juárez-Vega. Guillermo G; Meza-Sánchez. David D; Hernández-Gilsoul. Thierry T; Tapia-Rodríguez. Miguel M; Gómez-Martín. Diana D
Key Findings
- Severe COVID‑19 patients have a higher proportion of low‑density granulocytes that produce NETs
- Plasma levels of LL‑37, neutrophil elastase and HMGB1‑DNA complexes are elevated in severe cases
- Blood from severe patients degrades NETs poorly, which can be improved by adding DNase
Practical Outcomes
- For biohackers, the findings mainly serve as a biomarker insight—higher LL‑37 signals severe disease, but there’s no direct protocol to modify LL‑37 or NETs. Monitoring LL‑37 isn’t currently actionable for health optimization, and interventions like DNase are not ready for DIY use.
Summary
The study shows that people with severe COVID-19 have more of a special type of white blood cell (low‑density granulocytes) that make sticky DNA webs called NETs, and they also have higher levels of the antimicrobial peptide LL‑37 in their blood, but the research doesn’t test any new treatments or give clear steps for self‑experiments.
Abstract
The coronavirus disease 2019 (COVID-19) is related to enhanced production of NETs, and autoimmune/autoinflammatory phenomena. We evaluated the proportion of low-density granulocytes (LDG) by flow cytometry, and their capacity to produce NETs was compared with that of conventional neutrophils. NETs and their protein cargo were quantified by confocal microscopy and ELISA. Antinuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and the degradation capacity of NETs were addressed in serum. MILLIPLEX assay was used to assess the cytokine levels in macrophages' supernatant and serum. We found a higher proportion of LDG in severe and critical COVID-19 which correlated with severity and inflammatory markers. Severe/critical COVID-19 patients had higher plasmatic NE, LL-37 and HMGB1-DNA complexes, whilst ISG-15-DNA complexes were lower in severe patients. Sera from severe/critical COVID-19 patients had lower degradation capacity of NETs, which was reverted after adding hrDNase. Anti-NET antibodies were found in COVID-19, which correlated with ANA and ANCA positivity. NET stimuli enhanced the secretion of cytokines in macrophages. This study unveils the role of COVID-19 NETs as inducers of pro-inflammatory and autoimmune responses. The deficient degradation capacity of NETs may contribute to the accumulation of these structures and anti-NET antibodies are related to the presence of autoantibodies.
Study Information
pubmed
2021
2021-09-26T00:00:00.000Z
10.3390/cells10102545
49
68