Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients

Holter, Jan Cato; Pischke, Søren Erik; Boer, Eline de; Lind, Andreas; Jenum, Synne; Holten, Aleksander Rygh; Tonby, Kristian; Barratt‐Due, Andreas; Sokolova, Marina; Schjalm, Camilla; Chaban, Viktoriia; Kolderup, Anette; Tran, Trung; Gjølberg, Torleif Tollefsrud; Skeie, Linda Gail; Hesstvedt, Liv; Ormåsen, Vidar; Fevang, Børre; Austad, Cathrine; Müller, Karl Erik; Fladeby, Cathrine; Holberg-Petersen, Mona; Halvorsen, Bente; Müller, Fredrik; Aukrust, Pål; Dudman, Susanne; Ueland, Thor; Andersen, Jan Terje; Lund‐Johansen, Fridtjof; Heggelund, Lars; Dyrhol‐Riise, Anne Ma; Mollnes, Tom Eirik

doi:10.1073/pnas.2010540117

Cited by 314 publications

(353 citation statements)

References 46 publications

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“…14 Complement activation has been associated with the excessive inflammatory response seen in patients with severe COVID-19, and the presence of a complement-mediated microvascular injury syndrome has been proposed based on the observed pattern of tissue damage. [11][12][13] SARS-CoV-2 is thought to predominantly trigger the lectin and alternative complement pathways, although the classical complement pathway could also be activated in this setting by immune complexes. 116 The C3a and C5a anaphylatoxins are potent inflammatory mediators and chemoattractants.…”

Section: Convergent Immunopathogenic Mechanisms Of Covid-19 and Slementioning

confidence: 99%

“…This is not known, however, and even if true, it could be offset by other sociodemographic, biologic, and clinical aspects of the disease and its management. In addition, excessive complement activation with consequent development of thrombotic microangiopathy D 1 0 4 X Xhas been identified in many patients with COVID-19 and seems to at least partially mediate organ dysfunction in severe cases, resembling a complement-mediated thrombotic microangiopathy.D 1 0 5 X X 11,12 Although complement consumption is a classic feature of SLE, the classical pathway is often the main target of activation by immune complexes in SLE, whereas the alternative and lectin-based complement pathways seem to play a greater role in COVID-19 pathogenesis. 13,14 There have been substantial scientific efforts around the world to elucidate COVID-19 pathogenesis, risk factors, optimal management, and prevention strategies.…”

Section: Introductionmentioning

confidence: 99%

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COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

Fernández-Ruiz

Paredes

Niewold

2021

Translational Research

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As the world navigates the Coronavirus disease 2019 (COVID-19) pandemic, there is a growing need to assess its impact in patients with autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE). Patients with SLE are a unique population when considering the risk of contracting COVID-19 and infection outcomes. The use of systemic glucocorticoids and immunosuppressants, and underlying organ damage from SLE are potential susceptibility factors. Most patients with SLE have evidence of high type I IFN activity, which may theoretically act as an antiviral line of defense or contribute to the development of a deleterious hyperinflammatory response in COVID-19. Other immunopathogenic mechanisms of SLE may overlap with those described in COVID-19, and thus studies in SLE could provide some insight into immune responses occurring in severe cases of the viral infection. We reviewed the literature to date on COVID-19 in patients with SLE and provide an in-depth review of current research in the area, including immune pathway activation, epidemiology, clinical features, outcomes, and the psychosocial impact of the pandemic in those with autoimmune disease.

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Section: Convergent Immunopathogenic Mechanisms Of Covid-19 and Slementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

Fernández-Ruiz

Paredes

Niewold

2021

Translational Research

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“…Eriksson et al (124) reported that MBL contributed to pathological thrombosis and coagulopathy (but not other organ dysfunction or intensity of inflammation) in critically ill COVID-19 patients. In contrast, Holter et al (125) did not find much difference in MBL concentrations in plasma between COVID-19 patients and controls although a transient increase of its level (at days 3-5 after hospital admission) was noted. It should be however stressed that narsoplimab, specifically targeting MASP-2, has recently been demonstrated to be a promising therapeutic agent, reducing detrimental effects of complement activation and giving no adverse reactions itself (126).…”

Section: Possible Associations Of Complement Activation Via the Lectimentioning

confidence: 75%

The Influence of the Lectin Pathway of Complement Activation on Infections of the Respiratory System

Świerzko

Cedzyński

2020

Front. Immunol.

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Lung diseases are among the leading causes of morbidity and mortality. Complement activation may prevent a variety of respiratory infections, but on the other hand, could exacerbate tissue damage or contribute to adverse side effects. In this review, the associations of factors specific for complement activation via the lectin pathway (LP) with infections of the respiratory system, from birth to adulthood, are discussed. The most extensive data concern mannose-binding lectin (MBL) which together with other collectins (collectin-10, collectin-11) and the ficolins (ficolin-1, ficolin-2, ficolin-3) belong to patternrecognition molecules (PRM) specific for the LP. Those PRM form complexes with MBLassociated serine proteases (MASP-1, MASP-2, MASP-3) and related non-enzymatic factors (MAp19, MAp44). Beside diseases affecting humanity for centuries like tuberculosis or neonatal pneumonia, some recently published data concerning COVID-19 are summarized.

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“…However, an exaggerated cytokine storm and dysregulation of the complement system is described in severe COVID-19. 36 , 37 This warrants further investigation related to the causes to the increased perioperative risk.…”

Section: Discussionmentioning

confidence: 95%

A Risk Model of Admitting Patients With Silent SARS-CoV-2 Infection to Surgery and Development of Severe Postoperative Outcomes and Death

Søreide

Yaqub²,

Hallet

et al. 2020

Annals of Surgery

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Objective: To model the risk of admitting silent COVID-19-infected patients to surgery with subsequent risk of severe pulmonary complications and mortality. Summary Background Data: With millions of operations cancelled during the COVID-19 pandemic, pressure is mounting to reopen and increase surgical activity. The risk of admitting patients who have silent SARS-Cov-2 infection to surgery is not well investigated, but surgery on patients with COVID-19 is associated with poor outcomes. We aimed to model the risk of operating on nonsymptomatic infected individuals and associated risk of perioperative adverse outcomes and death. Methods: We developed 2 sets of models to evaluate the risk of admitting silent COVID-19-infected patients to surgery. A static model let the underlying infection rate (R rate) and the gross population-rate of surgery vary. In a stochastic model, the dynamics of the COVID-19 prevalence and a fixed population-rate of surgery was considered. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 90% uncertainty limits. The modelling was applied for high-income regions (eg, United Kingdom (UK), USA (US) and European Union without UK (EU27), and for the World (WORLD) based on the WHO standard population. Results: Both models provided concerning rates of perioperative risk over a 24-months period. For the US, the modelled rates were 92,000 (UI 68,000–124,000) pulmonary complications and almost 30,000 deaths (UI 22,000–40·000), respectively; for Europe, some 131,000 patients (UI 97,000–178,000) with pulmonary complications and close to 47,000 deaths (UI 34,000–63,000) were modelled. For the UK, the model suggested a median daily number of operations on silently infected ranging between 25 and 90, accumulating about 18,700 (UI 13,700–25,300) perioperative pulmonary complications and 6400 (UI 4600–8600) deaths. In high-income regions combined, we estimated around 259,000 (UI 191,000–351,000) pulmonary complications and 89,000 deaths (UI 65,000–120,000). For the WORLD, even low surgery rates estimated a global number of 1.2 million pulmonary complications and 350,000 deaths. Conclusions: The model highlights a considerable risk of admitting patients with silent COVID-19 to surgery with an associated risk for adverse perioperative outcomes and deaths. Strategies to avoid excessive complications and deaths after surgery during the pandemic are needed.

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Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients

Cited by 314 publications

References 46 publications

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

The Influence of the Lectin Pathway of Complement Activation on Infections of the Respiratory System

A Risk Model of Admitting Patients With Silent SARS-CoV-2 Infection to Surgery and Development of Severe Postoperative Outcomes and Death

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