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.
Highlights
Since December 2019 the SARS-CoV-2 has spread throughout the world infecting dozens of millions of people and resulting in over 2.8 million deaths, as of April 2021
Long et al showed that asymptomatic individuals presented with significantly longer duration of viral shedding compared to symptomatic patients, lower levels of IgG antibodies to SARS-CoV-2, and lower serum levels of 18/48 cytokines, including interferon-gamma levels, suggesting that asymptomatic individuals displayed a weaker anti-virus-reactive immune response to SARS-CoV-2 [15]
Individuals were considered asymptomatic in the absence of any symptoms since the onset of the pandemic, according to a detailed history obtained by a physician
Summary
Since December 2019 the SARS-CoV-2 has spread throughout the world infecting dozens of millions of people and resulting in over 2.8 million deaths, as of April 2021. The proportion of asymptomatic individuals varies widely among different viral infections, whereas relevant biomarkers do not currently exist due to our limited knowledge of the molecular host-pathogen interactions and immune response to particular infections [8]. The reasons why certain individuals, including even people living with HIV [11] or other immunodeficiencies [12], do not develop clinical symptoms during SARS-CoV-2 infection are essentially unknown [13, 14]. Long et al showed that asymptomatic individuals presented with significantly longer duration of viral shedding compared to symptomatic patients, lower levels of IgG antibodies to SARS-CoV-2, and lower serum levels of 18/48 cytokines, including interferon-gamma levels, suggesting that asymptomatic individuals displayed a weaker anti-virus-reactive immune response to SARS-CoV-2 [15]. Chan et al showed in a whole blood transcriptomic analyses that asymptomatic patients display a less robust response to type-I interferon than symptomatic patients, whereas differences between asymptomatic and symptomatic patients may be present at the cellular, innate, and adaptive immune response levels [16]
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