Dysregulated transcriptional responses to SARS-CoV-2 in the periphery

Abstract

SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92–0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.

An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility

“…Transcriptomics of COVID-19 peripheral blood was generated by a previous study as described [ 24 ]. For that study [ 24 ], samples were collected as part of the Molecular and Epidemiological Study of Suspected Infection (MESSI), which was conducted at Duke University Health System (DUHS) and the Durham Veterans Affairs Health Care System (DVAHCS). SARS-CoV-2 RT-PCR testing was used to confirm infection status.…”

“…At enrollment (day 0), date of symptom onset was determined, and an initial symptom survey recorded maximum score for each symptom category between symptom onset and study enrollment. Samples used for blood transcriptomics of acute respiratory infection due to seasonal coronavirus, influenza, or bacterial pneumonia, and healthy controls were also previously described [ 24 ]. Total RNA was extracted from peripheral whole blood, and cDNA libraries prepared using NuGEN Universal Plus mRNA-seq with AnyDeplete Globin reduction were sequenced on the Illumina NovaSeq 6000, as described [ 24 ].…”

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents

“…We obtained previously collected sera from subjects enrolled in the Duke University Molecular and Epidemiological Study of Suspected Infection (MESSI) 42 Informed consent was obtained from all study participants, with written approval obtained using an electronic consent document. Mild disease was defined as any PCR-confirmed infection that did not require hospitalization.…”

Sera proteomic features of active and recovered COVID-19 patients: potential diagnostic and prognostic biomarkers

“…Among these antibodies, IGLC2, IGLC7, IGLV3-10, and IGLV3-19 had been previously reported to be upregulated in the B-cells of COVID-19 patients during COVID-19 pneumonia, and IGLC7 had been selected as a marker to distinguish severe and non-severe cases of COVID-19. 4 Cluster 3, consisting of proteins upregulated in the COVID-19 patient compared to the HDs and recovered COVID-19 patient groups. As the expression of these proteins was upregulated after SARS-CoV-2 infection, while returned to HDs levels after recovery, they might be potential prognosis biomarkers.…”