Inflammation-type dysbiosis of the oral microbiome associates with the duration of COVID-19 symptoms and long COVID

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the pandemic Coronavirus Disease 2019 and now many face the burden of prolonged symptoms-long-lasting COVID-19 symptoms or "long-COVID". Long-COVID is thought to be linked to immune dysregulation due to harmful inflammation, with the exact causes being unknown. Given the role of the microbiome in mediating inflammation, we aimed to examine the relationship between the oral microbiome and the duration of long-COVID symptoms. Tongue swabs were collected from patients presenting with symptoms concerning for COVID-19. Confirmed infections were followed until resolution of all symptoms. Bacterial composition was determined by metagenomic sequencing. We used random forest modeling to identify microbiota and clinical covariates that associated with long-COVID symptoms. Of the patients followed, 63% (17/27) developed ongoing symptomatic COVID-19 and 37% (10/27) went on to long-COVID. Patients with prolonged symptoms had significantly higher abundances of microbiota that induce inflammation, such as members of the genera Prevotella and Veillonella. Of note are species that produce lipopolysaccharides and the similarity of long-COVID patients' oral microbiome to those of patients with chronic fatigue syndrome. All together, we our findings suggest an association with the oral microbiome and long-COVID revealing the possibility that dysfunction of the oral microbiome may contribute to this draining disease.

Oral Prevotella Species and Their Connection to Events of Clinical Relevance in Gastrointestinal and Respiratory Tracts

“…Changes in abundance were seen also for several Prevotella species, such as P. denticola , P. oris , P. jejuni , P. intermedia , P. melaninogenica , P. fusca , and P. scopos , which were among the 37 species distinctive for the healthy and diseased individuals, and most of them separated the symptomatic COVID-19 and non-COVID groups from each other ( Xiong et al, 2021 ). A dysbiotic oropharyngeal microbiota with gram-negative commensals, considered pathobionts due to their lipopolysaccharide production, has been connected to a so-called long-COVID disease ( Haran et al, 2021 ). Among 164 patients with various types of symptoms, increased abundances of several Prevotella species were among the top predicting taxa from swabs of the posterior oropharynx: P. denticola , P. nigrescens , P. histicola , and P. oulorum in the patient group with ongoing symptoms, and P. denticola , P. melaninogenica , P. jejuni , and P. nigrescens in the determined long-COVID group ( Haran et al, 2021 ).…”

“…A dysbiotic oropharyngeal microbiota with gram-negative commensals, considered pathobionts due to their lipopolysaccharide production, has been connected to a so-called long-COVID disease ( Haran et al, 2021 ). Among 164 patients with various types of symptoms, increased abundances of several Prevotella species were among the top predicting taxa from swabs of the posterior oropharynx: P. denticola , P. nigrescens , P. histicola , and P. oulorum in the patient group with ongoing symptoms, and P. denticola , P. melaninogenica , P. jejuni , and P. nigrescens in the determined long-COVID group ( Haran et al, 2021 ). Sulaiman et al (2021) examined a hospitalized cohort of 589 critically ill COVID-19 patients, characterizing their lung microbiome from bronchoalveolar lavage samples.…”

Pros and Cons of CAD/CAM Technology for Infection Prevention in Dental Settings during COVID-19 Outbreak

“…These features are very important for COVID-19 prevention, and in particular, for special care dentistry, dental care on non-responder patients to COVID-19 vaccinations, and face to face care in patients affected by long-COVID-19 syndromes [ 71 ]. Long-COVID-19 syndromes are largely unknown, but at least two features are relevant to dentistry: breathlessness (25% of cases) and dysfunction of the oral microbiome [ 13 , 71 ].…”

“…More efficiency and cost-effectiveness seem to be promising for the reduction of dental costs for patients and improving oral health and wellness to cover the population’s need [ 2 , 3 , 69 ]. Nevertheless, the development of the professional harmonization and ergonomics of the “human-technical complex dental office system” is necessary in light of the newly emerging infectious agents, the health service disruption, the expected aggravation of the prevalence of infectious agents ( Mycobacterium tuberculosis , drug-resistant infective agents), well known in dentistry, and the supposed endemic fate of COVID-19 [ 13 , 77 , 78 ].…”

“…Unfortunately, asymptomatic cases are nearly impossible to identify by triage in a dental setting. SARS-CoV-2 causes or influences different oral manifestations, with multiple clinical aspects and oral microbiome derangement [ 13 , 14 ]. Recently, it has been reported that dental biofilm also harbours SARS-CoV-2 RNA from symptomatic COVID-19 patients [ 15 , 16 ].…”