Metatranscriptomic Characterization of Coronavirus Disease 2019 Identified a Host Transcriptional Classifier Associated With Immune Signaling

Abstract

BACKGROUND The recent identification of a novel coronavirus, also known as SARS-CoV-2, has caused a global outbreak of respiratory illnesses. The rapidly developing pandemic has posed great challenges to diagnosis of this novel infection. However, little is known about the metatranscriptomic characteristics of patients with Coronavirus Disease 2019 (COVID-19). METHODS We analyzed metatranscriptomics in 187 patients (62 cases with COVID-19 and 125 with non-COVID-19 pneumonia). Transcriptional aspects of three core elements – pathogens, the microbiome, and host responses – were interrogated. Based on the host transcriptional signature, we built a host gene classifier and examined its potential for diagnosing COVID-19 and indicating disease severity. RESULTS The airway microbiome in COVID-19 patients had reduced alpha diversity, with 18 taxa of differential abundance. Potentially pathogenic microbes were also detected in 47% of the COVID-19 cases, 58% of which were respiratory viruses. Host gene analysis revealed a transcriptional signature of 36 differentially expressed genes significantly associated with immune pathways such as cytokine signaling. The host gene classifier built on such a signature exhibited potential for diagnosing COVID-19 (AUC of 0.75-0.89) and indicating disease severity. CONCLUSIONS Compared to those with non-COVID-19 pneumonias, COVID-19 patients appeared to have a more disrupted airway microbiome with frequent potential concurrent infections, and a special trigger host immune response in certain pathways such as interferon gamma signaling. The immune-associated host transcriptional signatures of COVID-19 hold promise as a tool for improving COVID-19 diagnosis and indicating disease severity.

Clinical practices underlie COVID-19 patient respiratory microbiome composition and its interactions with the host

“…Importantly, several of the taxa reported to change between intubated and nonintubated patients were reported to be linked to diagnosis in previous COVID-19 microbiome studies [15][16][17] . In our study, no taxa were differentially abundant between COVID-19 positive and negative patients after controlling for patient intubation.…”

“…Previous studies exploring other pulmonary disorders have shown that lung microbiota may exacerbate their symptoms and contribute to their severity 13 , potentially through direct crosstalk with the immune system and/or due to bacteremia and secondary infections 14 . Few studies of the respiratory microbiome in COVID-19 have revealed elevated levels of opportunistic pathogenic bacteria [15][16][17] . However, reports on bacterial diversity are contradictory.…”

IFN-γ is an independent risk factor associated with mortality in patients with moderate and severe COVID-19 infection

“…In cardiomyocytes, there is an up-regulation of genes responsible for IFN-γ suppression, also suggesting an effect IFN-γ in the cardiac function, in a sepsis-like pattern [ 28 ]. Furthermore, the relationship of IFN-γ disruption is not only associated with COVID-19 and the immune system, but there is a relationship of microbiome modification, altering the cell transcriptome with gene overexpression, which can be associated with the cytokine storm [ 29 , 30 ].…”

Gastrointestinal symptoms associated with COVID-19: impact on the gut microbiome

“…Furthermore, in another study with 62 COVID-19 patients was found a reduced alpha diversity in microbes. 75 The metatranscriptional analysis revealed that there were 36 differentially genes associated with immune pathways and cytokine signaling related to the diagnosis and severity of COVID-19, such as interferon-gamma signaling. 74 Despite reporting interesting patterns, the studies mentioned above are not without limitations.…”