Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was identified in China in 2019 as the causative agent of COVID-19, and quickly spread throughout the world, causing over 7 million deaths, of which 2 million occurred prior to the introduction of the first vaccine. In the following discussion, while recognising that complement is just one of many players in COVID-19, we focus on the relationship between complement and COVID-19 disease, with limited digression into directly-related areas such as the relationship between complement, kinin release, and coagulation. Prior to the 2019 COVID-19 outbreak, an important role for complement in coronavirus diseases had been established.

Alternative pathway activation in pregnancy, a measured amount "complements" a successful pregnancy, too much results in adverse events.

During pregnancy, the maternal host must adapt in order to enable growth of the fetus. These changes affect all organ systems and are designed both to protect the fetus and to minimize risk to the mother. One of the most prominent adaptations involves the immune system.

The susceptibility of the kidney to alternative pathway activation-A hypothesis.

The glomerulus is often the prime target of dysregulated alternative pathway (AP) activation. In particular, AP activation is the key driver of two severe kidney diseases: atypical hemolytic uremic syndrome and C3 glomerulopathy. Both conditions are associated with a variety of predisposing molecular defects in AP regulation, such as genetic variants in complement regulators, autoantibodies targeting AP proteins, or autoantibodies that stabilize the AP convertases (C3- and C5-activating enzymes).

Evaluation of CME Arrival Prediction Using Ensemble Modeling Based on Heliospheric Imaging Observations.

In this study, we evaluate a coronal mass ejection (CME) arrival prediction tool that utilizes the wide-angle observations made by STEREO's heliospheric imagers (HI). The unsurpassable advantage of these imagers is the possibility to observe the evolution and propagation of a CME from close to the Sun out to 1 AU and beyond. We believe that by exploiting this capability, instead of relying on coronagraph observations only, it is possible to improve today's CME arrival time predictions.

Professor Sir Peter J. Lachmann, FRS, FMedSci (1931-2020).

As members of the International Complement Society (ICS) will be aware, Professor Sir Peter Lachmann sadly passed away, peacefully and at home, on 26th December 2020 [...

Discovery of 4-((2,4)-4-Ethoxy-1-((5-methoxy-7-methyl-1-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases.

The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several human diseases including age-related macular degeneration, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and various glomerular diseases. The serine protease factor B (FB) is a key node in the AP and is integral to the formation of C3 and C5 convertase. Despite the prominent role of FB in the AP, selective orally bioavailable inhibitors, beyond our own efforts, have not been reported previously.

Complement and Bacterial Infections: From Molecular Mechanisms to Therapeutic Applications.

Complement is a complex protein network of plasma, and an integral part of the innate immune system. Complement activation results in the rapid clearance of bacteria by immune cells, and direct bacterial killing via large pore-forming complexes. Here we review important recent discoveries in the complement field, focusing on interactions relevant for the defense against bacteria.

The properdin pathway: an "alternative activation pathway" or a "critical amplification loop" for C3 and C5 activation?

This review is not intended to cover in detail all aspects of the discovery and evolution of our understanding of the "alternative pathway" of complement activation, there are many excellent reviews that do this (see Fearon (CRC Crit Rev Immunol 1:1-32, 1979), Pangburn and Müller-Eberhard (Springer Semin Immunopathol 7:163-192, 1984)), but instead to give sufficient background for current concepts to be put in context. The prevailing textbook view, of components having a primary role as an alternative "pathway" for C3 activation, is challenged, with an argument developed for the primary role of the system being that of providing a surface-dependent amplification loop for both C3 and C5 activation. Whatever the mechanism by which the initial C3b molecule is generated, deposition onto a surface has the potential to target that surface for elimination.

Utility of the Surgical Apgar Score in a district general hospital.

Background: The Surgical Apgar Score (SAS) is a simple tool for intraoperative risk stratification. The aim of this prospective observational study was to assess its performance in predicting outcome after general/vascular and orthopedic surgery and its utility in a U.K.

Medical response planning for pandemic flu.

This quantitative research study evaluates the health care infrastructure necessary to provide medical care in US hospitals during a flu pandemic. These hospitals are identified within the US health care system because they operate airborne infectious isolation rooms. Data were obtained from the 2006 American Hospital Association annual survey.

Role of information technology in disaster medical response.

This article addresses the importance of information technology (IT) in support of disaster medical response and provides a framework for the use of IT in response to natural disasters or terrorist activities. The appropriate use of IT enhances the effectiveness of the disaster response system, thereby safeguarding the population and the community infrastructure. This study found that most US hospitals have wireless local area networks (LANs) with disaster medical response capabilities.

The magnetic Sun.

The nature of our star, the Sun, is dominated by its complex and variable magnetic fields. It is the purpose of this paper to review the fundamental nature of our magnetic Sun by outlining the most basic principles behind the way the Sun works and how its fields are generated, and to examine not only the historical observations of our magnetic star, but, in particular, to study the wonderful observations of the Sun being made from space today. However, lying behind all of this are the most basic equations derived by James Clerk Maxwell, describing how the magnetic fields and plasmas of our Sun's atmosphere, and indeed of all stellar atmospheres, work and how they influence the Earth.

Plain abdominal radiographs: can we interpret them?

Introduction: Plain abdominal radiographs commonly form a part of medical assessments. Most of these films are interpreted by the clinicians who order them. Interpretation of these films plays an important diagnostic role and, therefore, influences the decision for admission and subsequent management of these patients.

Can histopathologic assessment of circumferential margin after preoperative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for 3-year disease-free survival?

Purpose: This study set out to determine the impact of a positive circumferential resection margin (CRM) (R1-R2) and pathologic downstaging on local recurrence and survival in patients with borderline resectable or unresectable rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy (CRT).

Methods And Materials: A total of 150 patients with locally advanced rectal cancer were treated with long-course neoadjuvant CRT using low-dose folinic acid and 5-fluorouracil. CRT was followed 6-12 weeks later by surgical excision.

Effect of complement fragment 1 esterase inhibition on survival of human decay-accelerating factor pig lungs perfused with human blood.

Background: The role of complement in hyperacute lung xenograft rejection has not been fully elucidated. The present study evaluates the effect of complement (C) 1 esterase inhibition on hyperacute rejection of human decay-accelerating factor (hDAF)-positive pig lung by human blood.

Methods: Using a modification of an established ex vivo model, right and left lungs from individual animals were surgically isolated and separately perfused.