Long COVID Linked With Altered Airway Microbiome

— Large observational study shows differences in oral, sputum bacterial diversity

Oral and sputum microbiomes appeared substantially different with long COVID, a large registry study showed.

The biggest reduction in richness and evenness of the variety of bacterial genus representation correlated with the worst symptoms around 6 months after the acute phase of the infection. For the very severe impairment patients, diversity indices for oral bacteria ranged from -0.02 to -3.57 (P≤0.001 to 0.03) and for sputum bacteria ranged from -0.03 to -0.12 (P=0.01 to 0.04) compared with mild impairment patients.

People whose long COVID symptoms included reduced lung function had a distinct oral microbiota profile, as did those with persistent neurocognitive symptoms. Gastrointestinal symptoms from long COVID correlated instead with a distinct microbiota profile in sputum.

A shift toward lactic acid bacteria was associated with elevated blood inflammatory proteins, "identifying airway microbiota changes as a feature of long COVID," reported James Chalmers, MBChB, PhD, of the University of Dundee in Scotland, and colleagues in the European Respiratory Journalopens in a new tab or window.

"What we don't know is whether these changes came before a COVID infection, or whether the changes happened following a COVID infection," Chalmers said in a statement. "We also do not know what will happen to the microbiome in patients in subsequent years. We would love to know whether these changes get better with time."

"We urgently need to know what causes long COVID because it remains a major healthcare problem," he added. "Understanding what causes it could lead to better treatmentsopens in a new tab or window; the microbiome can be changed using antibiotics, probiotics, or other measures. We hope our findings will stimulate more research into long COVID and in the future, we would love to see treatment trials to help people with this devastating condition."

The U.K. Post-hospitalisation COVID-19 (PHOSP-COVID) study included 771 adults who had been prospectively recruited to the longitudinal study after an inpatient stay for the infection and had their microbiota assessed via oral rinse and spontaneous sputum at a median of 6 months post-discharge. Mean age of participants was 57.5, and 38.5% were women.

Findings were adjusted for age, sex, body mass index, number of comorbidities, presence of respiratory comorbidities, antibiotic treatment during hospitalization, smoker status, and World Health Organization clinical progression score.

Differential abundance analysis pointed to a reduction in relative abundance with long COVID severity for 10 genera of bacteria, including four oral commensals: Prevotella, Neisseria, Haemophilus, and Fusobacterium. There was an increase in relative abundance with long COVID severity for other commensal oral genera: Streptococcus, Rothia, Veillonella, and Limosilactobacillus.

"These taxa have been reported as being differently abundant in several oral microbiota studies of acute COVID-19, observed discordances likely reflect differences in study design," the researchers noted. "The overlap between our findings and these studies at the time of infection suggest a possible medium-term sustained pulmonary microbiota alteration post-COVID-19."

The group cautioned that their study could not determine causality, and the lack of pre-COVID samples and a non-COVID control group meant they couldn't differentiate microbiota differences due to hospitalization or general respiratory illness alone. Generalizability to persons who were less ill during the acute phase of infection wasn't clear either.

However, from this study and others, "both microbiota profile differences and chronic inflammation appear to be key components of ongoing COVID-19," Chalmers and colleagues wrote. "Similar to bronchiectasis, a form of vicious cycle may exist where inflammation drives microbiota profile shifts which in turn drives inflammation. Mechanistic studies are needed to better understand the microbiota-inflammation relationship, to ascertain whether this could be a viable therapeutic target in [long COVID]."