@article{2999745,
    title = "Blood Transcriptomes of Anti-SARS-CoV-2 Antibody-Positive Healthy Individuals Who Experienced Asymptomatic Versus Clinical Infection",
    author = "Sfikakis, P.P. and Verrou, K.-M. and Ampatziadis-Michailidis, G. and Tsitsilonis, O. and Paraskevis, D. and Kastritis, E. and Lianidou, E. and Moutsatsou, P. and Terpos, E. and Trougakos, I. and Chini, V. and Manoloukos, M. and Moulos, P. and Pavlopoulos, G.A. and Kollias, G. and Hatzis, P. and Dimopoulos, M.A.",
    journal = "Frontiers in Immunology",
    year = "2021",
    volume = "12",
    publisher = "Frontiers Media S.A",
    doi = "10.3389/fimmu.2021.746203",
    keywords = "arachidonate 15 lipoxygenase;  coronavirus nucleocapsid protein;  coronavirus spike glycoprotein;  interferon;  SARS-CoV-2 antibody;  transcriptome;  messenger RNA;  transcriptome;  virus antibody, adult;  aged;  Article;  asymptomatic coronavirus disease 2019;  bioinformatics;  CACNA2D2 gene;  CLEC12A gene;  CLEC1B gene;  clinical article;  coronavirus disease 2019;  electrochemiluminescence immunoassay;  ENC1 gene;  female;  FOLR3 gene;  GCAT gene;  gene;  gene expression;  gene ontology;  gene set enrichment analysis;  genome-wide association study;  GZMH gene;  human;  IFI44L gene;  IFIT3 gene;  innate immunity;  Kyoto Encyclopedia of Genes and Genomes;  male;  PI3 gene;  real time reverse transcription polymerase chain reaction;  RNA isolation;  RNA sequencing;  RSAD2 gene;  asymptomatic infection;  blood;  gene expression profiling;  genetics;  immunology;  pathology;  sequence analysis;  severity of illness index, Adult;  Antibodies, Viral;  Asymptomatic Infections;  COVID-19;  Female;  Gene Expression Profiling;  Humans;  Immunity, Innate;  Male;  RNA, Messenger;  SARS-CoV-2;  Sequence Analysis, RNA;  Severity of Illness Index;  Transcriptome",
    abstract = "The reasons behind the clinical variability of SARS-CoV-2 infection, ranging from asymptomatic infection to lethal disease, are still unclear. We performed genome-wide transcriptional whole-blood RNA sequencing, bioinformatics analysis and PCR validation to test the hypothesis that immune response-related gene signatures reflecting baseline may differ between healthy individuals, with an equally robust antibody response, who experienced an entirely asymptomatic (n=17) versus clinical SARS-CoV-2 infection (n=15) in the past months (mean of 14 weeks). Among 12.789 protein-coding genes analysed, we identified six and nine genes with significantly decreased or increased expression, respectively, in those with prior asymptomatic infection relatively to those with clinical infection. All six genes with decreased expression (IFIT3, IFI44L, RSAD2, FOLR3, PI3, ALOX15), are involved in innate immune response while the first two are interferon-induced proteins. Among genes with increased expression six are involved in immune response (GZMH, CLEC1B, CLEC12A), viral mRNA translation (GCAT), energy metabolism (CACNA2D2) and oxidative stress response (ENC1). Notably, 8/15 differentially expressed genes are regulated by interferons. Our results suggest that subtle differences at baseline expression of innate immunity-related genes may be associated with an asymptomatic disease course in SARS-CoV-2 infection. Whether a certain gene signature predicts, or not, those who will develop a more efficient immune response upon exposure to SARS-CoV-2, with implications for prioritization for vaccination, warrant further study. © Copyright © 2021 Sfikakis, Verrou, Ampatziadis-Michailidis, Tsitsilonis, Paraskevis, Kastritis, Lianidou, Moutsatsou, Terpos, Trougakos, Chini, Manoloukos, Moulos, Pavlopoulos, Kollias, Hatzis and Dimopoulos."
}