Detection of autoimmune antibodies in severe but not in moderate or asymptomatic COVID-19 patients
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Abstract
The heterogeneity of COVID-19 lies within its diverse symptoms and severity, ranging from mild to lethal. Acute respiratory distress syndrome (ARDS) has been shown to be the leading cause of mortality in COVID-19 patients, characterized by a hyper cytokine storm. Autoimmunity is proposed to occur as a result of COVID-19, given the high similarity of the immune responses observed in COVID-19 and autoimmune diseases. Here, we investigate the level of autoimmune antibodies in COVID-19 patients with different severities. Initial screening for antinuclear antibodies (ANA) IgG revealed that 1.6% (2/126) and 4% (5/126) of ICU COVID-19 cases developed strong and moderate ANA levels, respectively. However, all the non-ICU cases (n=273) were ANA negative. The high ANA level was confirmed by immunofluorescence (IFA) and large-scale autoantibody screening by phage immunoprecipitation-sequencing (PhIP-Seq). Indeed, the majority of the samples showed “speckled” ANA pattern by microscopy, and we demonstrate that samples of ICU patients with strong and moderate ANA levels contain autoantibody specificities that predominantly targeted proteins involved in intracellular signal transduction, metabolism, apoptotic processes, and cell death; further denoting reactivity to nuclear and cytoplasmic antigens. In conclusion, our results further support the notion of routine screening for autoimmune responses in COVID-19 patients, which might help improve disease prognosis and patient management. Further, results provide compelling evidence that ANA-positive individuals should be excluded from being donors for convalescent plasma therapy in the context of Covid-19.
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SciScore for 10.1101/2021.03.02.21252438: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: 2.1 Sample collection and ethical compliance: This study was approved by the IRB committees of Hamad Medical Corporation (MRC-01-20-145) and Qatar University (QU-IRB 1289-EA/20). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources 2.6 Detection of shared linear B cell epitopes: To test for shared linear B cell epitopes between the identified autoantigens and SARS-CoV-2 antigens, we built a pairwise distance matrix that captured the maximum size of linear sequence identity of amino acids between the 79 differentially enriched human 90 aa … SciScore for 10.1101/2021.03.02.21252438: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: 2.1 Sample collection and ethical compliance: This study was approved by the IRB committees of Hamad Medical Corporation (MRC-01-20-145) and Qatar University (QU-IRB 1289-EA/20). Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources 2.6 Detection of shared linear B cell epitopes: To test for shared linear B cell epitopes between the identified autoantigens and SARS-CoV-2 antigens, we built a pairwise distance matrix that captured the maximum size of linear sequence identity of amino acids between the 79 differentially enriched human 90 aa peptides and 17 reference sequence of SARS-CoV2 proteins in UniProtKB (https://covid-19.uniprot.org) as previously described [12]. UniProtKBsuggested: (UniProtKB, RRID:SCR_004426)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Nevertheless, some limitations are associated with this study. First, the sample size is relatively small, and a larger-scale study may be needed. Second, some of the sera samples were only taken at one time point, which makes it harder to explore ANA change over time. Third, people are admitted to ICU mostly after 7 days after infection, so the time points of the ICU samples are calculated from their admission to ICU rather than the beginning of the infection. Thus, the acute vs. convalescent phase inconsistency of the ICU and non-ICU samples may affect the accuracy of the results. Still, this study provides a closer insight into the immunological progression of the disease and its prognosis. We, therefore, propose to include the screening for autoimmune antibodies as a routine test for COVID-19 patients.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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