Respiratory Co-Infections: Modulators of SARS-CoV-2 Patients’ Clinical Sub-Phenotype

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.

Nasopharyngeal Microbiome Community Composition and Structure Is Associated with Severity of COVID-19 Disease and Breathing Treatment

“…Finally, Clostridium botulinum, Bacillus cereus and Halomonas spp. were found in almost all samples in an Indian study focused on more severe COVID-19 [5], which was clearly incompatible with our findings. This study did not include COVID-19 negative controls, which may have helped to distinguish between species commonly found in the NP space for the region in which they were collected versus those that are enhanced or lost during SARS-CoV-2 infection.…”

“…In one study of co-infections in the respiratory tract (n = 100 positive) that found limited viral genetic variation among patients, the authors suggested that the presence of particular species (e.g., Clostridium botulinum, Bacillus cereus and Halomonas spp.) was potentially a more important factor on clinical outcomes [5]. While it is difficult to draw strong conclusions from this study due to a lack of control group, the observation underscores the need to understand whether SARS-CoV-2 infection enhances the respiratory tract for opportunistic coinfections or if an impoverished microbiome increases susceptibility to severe disease.…”

“…Although much research has been rapidly produced regarding the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, only a handful of studies have examined associations of viral infection with the nasopharyngeal (NP) microbiome [1][2][3][4][5]. It is hypothesized that SARS-CoV-2 infection may compromise immunity and increase bacterial attachment, growth, and possibly lead to co-infections or "super infections" [5,6]. Bacterial infection can further exacerbate inflammatory responses causing tissue damage and further dissemination of both the virus and bacteria [6].…”

Co-infections as Modulators of Disease Outcome: Minor Players or Major Players?

“…A classical case in point is the HIV infection, which compromises the host immune system thereby, making the host more susceptible to co-infection by other opportunistic pathogens. At the host level, inter-pathogen interactions may lead to altered disease epidemiology affecting the mortality and morbidity associated with an infectious disease ( Pandey et al, 2021 ; Figure 5 ). Co-infection increases the possibility of genetic recombination and reassortment leading to the emergence of novel antigenic variants thus affecting the efficacy of drugs, treatment regimen and vaccines.…”

Clinico-Genomic Analysis Reveals Mutations Associated with COVID-19 Disease Severity: Possible Modulation by RNA Structure

“…28289 from Norgen Biotek Corp, Thorold, ON, Canada), thoroughly mixed, and incubated at 37°C for 10 min. In-house sequencing and data analysis for the 196 SARS-CoV-2 genomes was performed using Oxford Nanopore Sequencing and Illumina-Miseq platforms and the pipelines used were the same as detailed in our prior studies [ 38 , 39 ].…”