Blood transcriptomes of anti-SARS-CoV2 antibody positive healthy individuals with prior asymptomatic versus clinical infection

Despite tremendous efforts by the international research community to understand the pathophysiology of SARS-CoV-2 infection, the reasons behind the clinical variability, ranging from asymptomatic infection to lethal disease, are still unclear. Existing inter-individual variations of the immune responses, due to environmental exposures and genetic factors, may be critical to the development or not of symptomatic disease after infection with SARS-CoV-2, and transcriptomic differences marking such responses may be observed even later, after convalescence. Herein, we performed genome-wide transcriptional whole-blood profiling to test the hypothesis that immune response-related gene signatures may differ between healthy individuals with prior entirely asymptomatic versus clinical SARS-CoV-2 infection, all of which developed an equally robust antibody response. Among 12.789 protein-coding genes analyzed, there were only six and nine genes with significantly decreased or increased expression, respectively, in those with prior asymptomatic infection (n=17, mean age 34 years) relatively to those with clinical infection (n=15, mean age 37 years). 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 an intrinsically weaker expression of some 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.