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Reviews of "Complement Dysregulation is a Predictive and Therapeutically Amenable Feature of Long COVID"

Reviewers: S Sacks (King's College London) | 📗📗📗📗◻️ • A Kulkarni (InFlaMed Inc) | 📘📘📘📘📘

Published onNov 28, 2023
Reviews of "Complement Dysregulation is a Predictive and Therapeutically Amenable Feature of Long COVID"
key-enterThis Pub is a Review of
Complement dysregulation is a predictive and therapeutically amenable feature of long COVID
Complement dysregulation is a predictive and therapeutically amenable feature of long COVID
Description

Background: Long COVID encompasses a heterogeneous set of ongoing symptoms that affect many individuals after recovery from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The underlying biological mechanisms nonetheless remain obscure, precluding accurate diagnosis and effective intervention. Complement dysregulation is a hallmark of acute COVID-19 but has not been investigated as a potential determinant of long COVID. Methods: We quantified a series of complement proteins, including markers of activation and regulation, in plasma samples from healthy convalescent individuals with a confirmed history of infection with SARS-CoV-2 and age/ethnicity/gender/infection/vaccine-matched patients with long COVID. Findings: Markers of classical (C1s-C1INH complex), alternative (Ba, iC3b), and terminal pathway (C5a, TCC) activation were significantly elevated in patients with long COVID. These markers in combination had a receiver operating characteristic predictive power of 0.794. Other complement proteins and regulators were also quantitatively different between healthy convalescent individuals and patients with long COVID. Generalized linear modeling further revealed that a clinically tractable combination of just four of these markers, namely the activation fragments iC3b, TCC, Ba, and C5a, had a predictive power of 0.785. Conclusions: These findings suggest that complement biomarkers could facilitate the diagnosis of long COVID and further suggest that currently available inhibitors of complement activation could be used to treat long COVID. Funding: This work was funded by the National Institute for Health Research (COV-LT2-0041), the PolyBio Research Foundation, and the UK Dementia Research Institute.

To read the original manuscript, click the link above.

Summary of Reviews: In this preprint, the authors evaluated differences in and the predictive power of complement proteins in Long COVID patients compared to those without.They further assess the potential of these biomarkers as therapeutic targets. Reviewers found this preprint to be reliable or strong, and investigating an under-studied area of COVID-19 research. According to reviewers, the methods were overall thorough and the paper well-developed. Some limitations identified were the inability of the study to fully assess mechanisms and drivers of complement differences, but the preprint still made important contributions and offers opportunities for further research questions. 

Reviewer 1 (Steven S…) | 📗📗📗📗◻️

Reviewer 2 (Amod K…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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