Temporal dynamics of oropharyngeal microbiome among SARS-CoV-2 patients reveals continued dysbiosis even after Viral Clearance

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has posed multiple challenges to global public health. Clinical features and sequela of SARS-CoV-2 infection include long-term and short-term complications often clinically indistinguishable from bacterial sepsis and acute lung infection. Post-hoc studies of previous SARS outbreaks postulate secondary bacterial infections with microbial dysbiosis. Oral microbial dysbiosis, particularly the altered proportion of Firmicutes and Proteobacteria, observed in other respiratory virus infection, like influenza, has shown to be associated with increased morbidity and mortality. Oropharynx and lung share similar kinds of bacterial species. We hypothesized that alteration in the Human Oropharyngeal Microbiome in SARS-CoV-2 patients can be a clinical indicator of bacterial infection related complications. We made a longitudinal comparison of oropharyngeal microbiome of 20 SARS-CoV-2 patients over a period of 30 days; at three time points, with a 15 days interval; contrasting them with a matched group of 10 healthy controls. Present observation indicates that posterior segment of the oropharyngeal microbiome is a key reservoir for bacteria causing pneumonia and chronic lung infection on SARS-CoV-2 infection. Oropharyngeal microbiome is indeed altered and its α-diversity decreases, indicating reduced stability, in all SARS-CoV-2 positive individuals right at Day-1; i.e. within ~24 h of post clinical diagnosis. The dysbiosis persists long-term (30 days) irrespective of viral clearance and/or administration of antibiotics. There is a severe depletion of commensal bacteria phyla like Firmicutes among the patients and that depletion is compensated by higher proportion of bacteria associated with sepsis and severe lung infection from phyla Proteobacteria. We also found elevated proportions of certain genus that have previously been shown to be causal for lung pneumonia in studies of model organisms and human autopsies’ including Stenotrophomonas, Acenetobactor, Enterobactor, Klebsiella and Chryseobacterium that were to be elevated among the cases. We also show that responses to the antibiotics (Azithromycin and Doxycycline) are not uniform for all individuals.

Integrated analysis reveals important differences in the gut and oropharyngeal microbiota between children with mild and severe hand, foot, and mouth disease

“…Our results also showed that the oropharyngeal microbiota in patients with severe HFMD was predominant in several bacterial genera, including Stenotrophomonas , Prevotella, and Streptococcus . The results are in line with several recent studies on oropharyngeal microbiota of patients with COVID-19 [ 41 , 42 ]. These bacteria were also observed in influenza virus-infected patients who often had secondary bacterial pneumonia.…”

“…Streptococcus is one of the most prevalent inhabitants of the oropharynx and respiratory tract of adults and children. Recent study has reported the reduction in proportion of Streptococcus and Velionella in COVID-19-infected patients compared to healthy control [ 41 ]. Prevotella members exhibit pro-inflammatory properties.…”

“…Stenotrophomonas is known as an organism with a low number of virulence factors, including efflux drug pumps, flagella, and siderophores, which cause opportunistic infections. Recently, Paine et al reported that it was significantly associated with COVID-19 infection [ 41 ]. Therefore, it remains to be studied whether these enriched bacterial genera could contribute to the progression and severity of HFMD.…”

Upper respiratory tract microbiome profiles in SARS-CoV-2 Delta and Omicron infected patients exhibit variant specific patterns and robust prediction of disease groups

“…In total, 43 COVID-19 patients (24 Delta and 19 Omicron) and 19 HC were recruited in this study. All 19 Omicron and 5 of the delta samples were collected by the clinicians of COM&JNM Hospital in Kalyani from December 2021 to January 2022 and the rest of the 19 Delta samples were collected from ICMR-Regional Medical Research Centre, Bhubaneswar during the COVID second wave and published recently by members of our group ( 28 ). Healthy controls were collected from Kalyani during November–Dec 2021.…”

A case of fulminant myocarditis associated with a novel coronavirus infection

“…Since the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) war, as of December 2021, COVID-19 has spread to 222 countries, resulting in more than 260 million con rmed cases and more than 5 million deaths worldwide 9 .The most common long-term effects and adverse consequences of SARS-CoV-2 infection are sepsis, pneumonia, and other pulmonary infections In fact, in addition to the possible direct infection of the heart muscle and other types of cardiovascular cells, the novel coronavirus can also mediate immune responses and in ammation, thus causing severe damage and dysfunction of the cardiovascular system.In the acute phase, the incidence of major all-cause cardiovascular diseases and mortality of COVID-infected patients increased signi cantly. Compared with uninfected patients, the risk of various cardiovascular diseases after "Yang" increased signi cantly by 330%, and the risk of allcause death was 81.1 times that of the former.…”