# Non-canonical Metatranscriptomic analysis of COVID-19 and Dengue reveals an expanded microbial and AMR landscape in COVID-19 mortality patients

## TL;DR

This study uses metatranscriptomics to show that viral infections like COVID-19 and dengue are linked to higher levels of antibiotic resistance genes, especially in severe cases.

## Contribution

The study reveals distinct resistome profiles and microbial communities in severe viral infections, emphasizing the role of antimicrobial resistance in disease progression.

## Key findings

- COVID-19 patients showed higher ARG abundance and microbial diversity compared to dengue.
- Key ARG hosts included Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii in severe cases.
- Beta-lactamase ARGs were common in both infections, with distinct gene variants in each disease.

## Abstract

AMR is a growing concern in viral infections, where microbiome shifts contribute to resistance gene dissemination. While dengue and COVID-19, caused by ssRNA viruses, are not bacterial-driven, their resistome and microbial communities influence disease progression and AMR burden. This study analyzes the resistome and microbiome in 251 COVID-19 and 112 dengue patients using non-canonical metatranscriptomics. By mapping antimicrobial resistance genes (ARGs) and their transcriptionally active microbes (TAMs) hosts, we uncover greater ARG burden in COVID-19, particularly during mortality, with a diverse set of associated TAMs compared to dengue. MDR genes were prevalent, with beta-lactamase ARGs commonly detected in both infections. COVID-19 exhibited higher carbapenemase resistance genes (NDM, OXA, VIM), while dengue was associated with TEM variants. Escherichia coli and Klebsiella pneumoniae were dominant ARG hosts, with Acinetobacter baumannii in COVID-19 mortality and Bacillus cereus in severe dengue. These findings highlight resistome dynamics and emphasize the need for AMR surveillance in high-burden infections.

Antibiotics are frequently administered to manage secondary complications in viral infections like COVID-19 and dengue, yet their broad usage can unintentionally amplify the resistome—the pool of antimicrobial resistance genes (ARGs)—within transcriptionally active microbes (TAMs). This aspect is often underexplored in non-bacterial infections. In this study, we analyzed human-unmapped reads from the transcriptomic data of 251 COVID-19 and 112 dengue patients to explore the active microbial community and their associated resistome profiles. Our findings reveal that both diseases harbor distinct and overlapping ARGs across multiple drug classes, including multidrug resistance (MDR) genes such as those conferring resistance to β-lactam antibiotics, which were detected in 49.5% of COVID-19 and 56.5% of dengue patients. Key resistant microbes included Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii in COVID-19, and Bacillus cereus in severe dengue. Notably, COVID-19 samples exhibited greater microbial diversity and ARG abundance compared to dengue, suggesting a stronger resistome influence on disease severity in COVID-19. These findings highlight the need to integrate resistome surveillance into the clinical management of viral infections, guiding more informed and targeted antibiotic use.