Abstract

Co-infection with ancillary pathogens is a significant modulator of morbidity and mortality in infectious diseases. There have been limited reports of co-infections accompanying SARS-CoV-2 infections, albeit lacking India specific study. The present study has made an effort toward elucidating the prevalence, diversity and characterization of co-infecting respiratory pathogens in the nasopharyngeal tract of SARS-CoV-2 positive patients. Two complementary metagenomics based sequencing approaches, Respiratory Virus Oligo Panel (RVOP) and Holo-seq, were utilized for unbiased detection of co-infecting viruses and bacteria. The limited SARS-CoV-2 clade diversity along with differential clinical phenotype seems to be partially explained by the observed spectrum of co-infections. We found a total of 43 bacteria and 29 viruses amongst the patients, with 18 viruses commonly captured by both the approaches. In addition to SARS-CoV-2, Human Mastadenovirus, known to cause respiratory distress, was present in a majority of the samples. We also found significant differences of bacterial reads based on clinical phenotype. Of all the bacterial species identified, ∼60% have been known to be involved in respiratory distress. Among the co-pathogens present in our sample cohort, anaerobic bacteria accounted for a preponderance of bacterial diversity with possible role in respiratory distress. Clostridium botulinum, Bacillus cereus and Halomonas sp. are anaerobes found abundantly across the samples. Our findings highlight the significance of metagenomics based diagnosis and detection of SARS-CoV-2 and other respiratory co-infections in the current pandemic to enable efficient treatment administration and better clinical management. To our knowledge this is the first study from India with a focus on the role of co-infections in SARS-CoV-2 clinical sub-phenotype.

Highlights

  • The COVID-19 disease that emerged in Wuhan, China has spread across the globe in the past 1 year and assumed pandemic proportions

  • For identification of co-infecting species we used two different Next generation sequencing (NGS) approaches: target amplification based on hybridisation capture (Illumina Respiratory Virus Oligo Panel (RVOP)) and whole transcriptome RNA-Seq (Holo-seq)

  • The present study utilized two different metagenomic approaches to identify the diversity of co-infecting species present within the upper respiratory tract of COVID-19 patients from the

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Summary

Introduction

The COVID-19 disease that emerged in Wuhan, China has spread across the globe in the past 1 year and assumed pandemic proportions. While the majority of patients with SARS-CoV-2 infection have mild to moderate symptoms, some progress to a severe disease category despite standard treatment regime (World Health Organization, 2020). Due to the diversity in clinical manifestations of the disease, more than one factor is assumed to possibly affect the clinical course of SARS-CoV-2 infection. A limited number of reports have indicated the presence of co-infections with viral and bacterial respiratory pathogens in SARS-CoV-2 infected individuals. Bacterial co-infections affect the morbidity and mortality in viral respiratory infections In this context, it is important to differentiate between hospital-acquired coinfection/secondary bacterial infection which develops during the course of hospitalization, versus an existing bacterial coinfection which is present when a patient reports to the hospital. Most of these findings are, associative in nature and do not clearly indicate whether co-infection is a driver of poor clinical outcomes, or more common in severe categories of patients (e.g., intubation associated pneumonia in patients on ventilatory support)

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