SARS-CoV-2 Infection Reduces Human Nasopharyngeal Commensal Microbiome with Inclusion of Pathobionts
Authors: Hoque Md. Nazmul , Sarkar Md. Murshed Hasan , Rahman M. Shaminur , Akter Shahina , Banu Tanjina Akhtar , Goswami Barna , Jahan Iffat , Hossain M. Saddam , Shamsuzzaman A. K. Mohammad , Nafisa Tasnim , Molla M. Maruf Ahmed , Yeasmin Mahmuda , Ghosh Asish Kumar , Osman Eshrar , Uzzaman Mohammad Samir , Habib Md Ahashan , Mahmud Abu Sayeed Mohammad , Crandall Keith A , Islam Tofazzal , Khan M. Salim 
Published: May 2021

Abstract
Background The SARS-CoV-2 primarily enters into the human body through nasopharyngeal tract (NT) and is the etiological agent of COVID-19. The microbiota of the NT may play a role in host immunity against respiratory infectious diseases. However, scant information is available on interactions of SARS-CoV-2 with the nasopharyngeal microbiome. To shed light on the effects and consequences of SARS-CoV-2 infection on microbiome diversity and composition, we conducted a high throughput RNA-Seq metagenomic investigation of 22 NT swab samples (including COVID-19 = 8, Recovered = 7, and Healthy = 7). Results This study for the first time demonstrates the association of microbiome diversity and their concomitant genomic features in the NT of COVID-19 and Recovered patients compared to Healthy humans, and discusses the role of the altered microbiomes in the pathophysiology of the SARS-CoV-2 infections. Our RNA-Seq metagenomic analyses detected 2281 bacterial species (including 1477, 919 and 676 in samples of Healthy human, COVID-19 and Recovered patients, respectively) indicating a distinct microbiome dysbiosis (COVID-19>Recovered>Healthy). The samples from COVID-19 patients and Recovered individuals had inclusion of 67% (including Streptococcus salivarius, S. mitis, Neisseria subflava, Veillonella dispar, Acinetobacter junii, Prevotella melaninogenica etc.) and 77% (including Pseudomonas stutzeri, Staphylococcus capitis, S. epidermidis, P. mendocina, Moraxella osloensis, A. indicus, Escherichia coli etc.) opportunistic pathogenic bacteria, respectively compared to Healthy individuals. Notably, 79% commensal bacteria (e.g., Pseudomonas sp. LPH1, Brevundimonas sp. Bb-A, P. oleovorans, Pseudomonas sp. phDV1, Brevundimonas sp. DS20, Idiomarinaceae bacterium HL-53, Alishewanella sp. 205, Sphingobacterium psychroaquaticum etc.) were found in healthy individuals but not detected in COVID-19 patients and Recovered individuals. Similar dysbiosis was also found in viral and archaeal fraction of the microbiomes. Although, 55 viral and 48 archaeal genera were detected, only 16% viral and 27% archaeal genera were shared across three metagenomes. We also detected altered metabolic pathways and functional genes including resistance to antibiotics and toxic compounds in the pathophysiology of COVID-19.Conclusions The nasopharyngeal microbiome dysbiosis and their genomic features in COVID-19, Recovered and Healthy individuals determined by our RNA-Seq analyses shed light on early interactions of SARS-CoV-2 with the nasopharyngeal resident microbiota that might be helpful for developing microbiome-based diagnostics and therapeutics for this novel pandemic disease.