The interplay between neutrophils, complement, and microthrombi in COVID-19

Zuo, Yu; Kanthi, Yogendra; Knight, Jason S.; Kim, Alfred H.J.

doi:10.1016/j.berh.2021.101661

Cited by 37 publications

(52 citation statements)

References 107 publications

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“…In COVID-19, NETs may be directly induced by SARS-CoV-2 ( 1 , 24 ). They may also be triggered indirectly via activated platelets and prothrombotic autoantibodies ( 1 , 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…In COVID-19, NETs may be directly induced by SARS-CoV-2 ( 1 , 24 ). They may also be triggered indirectly via activated platelets and prothrombotic autoantibodies ( 1 , 15 ). Once formed, NETs likely exert direct cytotoxic effects against pulmonary epithelium, resulting in alveolar damage and fibrosis ( 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…While it has been more than a year since the initial outbreak, coronavirus disease 2019 (COVID-19) — caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) — remains a global health challenge with alarming death tolls ( 1 ). Many survivors of COVID-19 continue to suffer from postacute sequelae of the infection, and the cause of these long-term symptoms remains, for the most part, unknown ( 2 – 4 ).…”

Section: Introductionmentioning

confidence: 99%

“…Many survivors of COVID-19 continue to suffer from postacute sequelae of the infection, and the cause of these long-term symptoms remains, for the most part, unknown ( 2 – 4 ). Severe acute COVID-19 is characterized by a thromboinflammatory state driven by a complex interplay between innate and adaptive immune responses ( 1 ). This state manifests clinically as acute respiratory distress syndrome and, in some patients, widespread thrombotic microangiopathy.…”

Section: Introductionmentioning

confidence: 99%

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Autoantibodies stabilize neutrophil extracellular traps in COVID-19

Zuo¹,

Yalavarthi²,

Navaz³

et al. 2021

JCI Insight

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The release of neutrophil extracellular traps (NETs) by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID-19. At the same time, a variety of functional autoantibodies have been observed in individuals with severe COVID-19 where they likely contribute to immunopathology. Here, we aimed to determine the extent to which autoantibodies might target NETs in COVID-19 and, if detected, to elucidate their potential functions and clinical associations. We measured anti-NET antibodies in 328 individuals hospitalized with COVID-19 alongside 48 healthy controls. We found high anti-NET activity in the IgG and IgM fractions of 27% and 60% of patients, respectively. There was a strong correlation between anti-NET IgG and anti-NET IgM (r=0.4, p<0.0001). Both anti-NET IgG and IgM tracked with high levels of circulating NETs, impaired oxygenation efficiency, and high circulating D-dimer. Furthermore, patients who required mechanical ventilation had a greater burden of anti-NET antibodies than did those not requiring oxygen supplementation. Levels of anti-NET IgG (and to a lesser extent anti-NET IgM) demonstrated an inverse correlation with the efficiency of NET degradation by COVID sera. Furthermore, purified IgG from COVID sera with high levels of anti-NET antibodies impaired the ability of healthy control serum to degrade NETs. In summary, many individuals hospitalized with COVID-19 have anti-NET antibodies, which likely impair NET clearance and may potentiate SARS-CoV-2-mediated thromboinflammation.

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“…In COVID-19, NETs may be directly induced by SARS-CoV-2 ( 1 , 24 ). They may also be triggered indirectly via activated platelets and prothrombotic autoantibodies ( 1 , 15 ).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Autoantibodies stabilize neutrophil extracellular traps in COVID-19

Zuo¹,

Yalavarthi²,

Navaz³

et al. 2021

JCI Insight

Self Cite

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“…Thrombogenic NETs elicited by the activated complement present in the blood of patients with COVID-19 [81] are candidates to amplify inflammation and thrombosis [154,155]. Anti-complement strategies based on eculizumab or AMY-101 have successfully been used in small numbers of severe and critical/intubated patients [156][157][158][159][160].…”

Section: Complement-based Therapiesmentioning

confidence: 99%

Patients with COVID-19: in the dark-NETs of neutrophils

et al. 2021

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SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.

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LF‐EMF Compound Block Type Signal Activates Human Neutrophilic Granulocytes In Vivo

Cuppen

Grădinaru²,

Sleuwen

et al. 2022

Bioelectromagnetics

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This research aims to demonstrate in a randomized, placebo‐controlled crossover design study that a nominal 5 μT low‐frequency electromagnetic field (LF‐EMF) signal for 30 min activates neutrophils in vivo in humans. Granularity of neutrophils was measured in blood samples of healthy human volunteers (n = 32) taken before and after exposure for both the exposure and control sessions. A significant decrease in the granularity, indicative of neutrophil activation, was observed both in the exposure measurements and the exposure minus control measurements. Earlier EMF publications show immune function increase in isolated cells and more effective immune responses in animals with infections. This result, therefore, supports the thesis that the exposure can activate the innate immune system in humans, speed up the innate immune response, and may have potential beneficial effects in infectious disease. © 2022 Bioelectromagnetics Society.

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The interplay between neutrophils, complement, and microthrombi in COVID-19

Cited by 37 publications

References 107 publications

Autoantibodies stabilize neutrophil extracellular traps in COVID-19

Autoantibodies stabilize neutrophil extracellular traps in COVID-19

Patients with COVID-19: in the dark-NETs of neutrophils

LF‐EMF Compound Block Type Signal Activates Human Neutrophilic Granulocytes In Vivo

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