AUTHOR=Huang Baozhen , Huang Jinghan , Chiang Nim Hang , Chen Zigui , Lui Grace , Ling Lowell , Kwan Mike Yat Wah , Wong Joshua Sung Chih , Mak Phoebe Qiaozhen , Ling Janet Wan Hei , Lam Ivan Cheuk San , Ng Rita Wai Yin , Wang Xingyan , Gao Ruonan , Hui David Shu-Cheong , Ma Suk Ling , Chan Paul K. S. , Tang Nelson Leung Sang 

TITLE=Interferon response and profiling of interferon response genes in peripheral blood of vaccine-naive COVID-19 patients

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1315602

DOI=10.3389/fimmu.2023.1315602

ISSN=1664-3224

ABSTRACT=Early reports indicated that interferon (IFN) responses were suppressed by the coronavirus (SARS-CoV-2) and clinical trials of administration of various kinds of interferons had been disappointing. Expression of interferon-stimulated genes (ISGs) in peripheral blood (better known as interferon score) has been a well-established bioassay marker of systemic IFN responses in autoimmune diseases. Therefore, with archival samples of a cohort of COVID-19 patients collected before the availability of vaccination, we aimed to better understand this innate immune response by studying the IFN score and related ISGs expression in bulk and single cell RNAs sequencing (scRNA-seq) expression datasets. In this study, we recruited 105 patients with COVID-19 and 30 healthy controls in Hong Kong. Clinical risk factors, disease course, and blood sampling times were recovered. Based on a set of five commonly used ISGs (IFIT1, IFIT2, IFI27, SIGLEC1, IFI44L), the IFN score was determined in blood leukocytes collected within 10 days after onset. Additional public datasets of bulk gene and scRNA-seq of blood samples were used for the validation. Compared to the healthy controls, we showed that ISGs expression and IFN score were significantly increased during the first 10 days after COVID infection in majority of patients (71%). Among those low IFN responders, they were more commonly asymptomatic patients (71% vs 25%). 22 patients did not mount an overall significant IFN response and were classified as low IFN responders (IFN score < 1). Both IFI27 and SIGLEC1 were monocyte-predominant expressing ISGs and IFI27 were activated even among those low IFN responders. In conclusion, a substantial IFN response was documented in this cohort of COVID-19 patients who experience a natural infection before the vaccination era. scRNA-seq data suggested monocytes were the cell-type that primarily accounted for the activation of two highly responsive ISGs genes (IFI44L and IFI27). As sampling time and age were two major confounders of ISG expression, they may account for contradicting observations among previous studies. On the other hand, the IFN score was not associated with the severity of the disease.