Two kinds of bacteria that naturally occur in the respiratory microbiome may help protect against long COVID when present in higher amounts, according to a new study published in Microbiology Spectrum. The findings highlight how differences in the bacterial composition of the upper respiratory tract may be linked to long-COVID severity.

For the study, researchers led by a team at the Universite Catholique de Louvain in Belgium analyzed nasal swab samples from 25 healthy participants, 24 influenza patients, and 107 patients with COVID-19 of different severities (50 moderate cases, 57 severe).

The presence of two bacteria—Dolosigranulum pigrum and Corynebacterium species—was tied to a lower risk of developing long COVID, or post-acute sequelae of SARS-CoV-2 (PASC). 

The findings highlight how differences in the bacterial composition of the upper respiratory tract may be linked to long-COVID severity.

“By examining microbiome samples from healthy people, influenza patients, and individuals with COVID-19 during acute and convalescent phases, we found that certain commensal bacteria, namely, Dolosigranulum pigrum (D. pigrum) and Corynebacterium species, were less abundant in individuals who developed long-COVID and more abundant in those who fully recovered,” the authors note. 

The study also tied antibiotic use to lower levels of protective bacteria, which may increase susceptibility to PASC.

“This study suggests that certain so-called protective bacteria in the respiratory microbiome may be associated with improved recovery following viral respiratory infections,” said the authors in a news release.

Beneficial bacteria ‘gatekeep’ against harmful pathogens

The upper respiratory tract is home to a complex community of microbes that, when in balance, boost the body’s immune response and make it harder for harmful pathogens to take hold. When those microbes are out of balance due to prior infections, asthma, or conditions like chronic obstructive pulmonary disease, it can worsen disease. 

The findings align with a growing body of research that suggests that some bacteria, such as Staphylococcus and Streptococcus, are associated with more severe COVID, while specific commensal bacteria (bacteria that live in or on a host without causing harm) are linked to milder cases. 

“The commensals frequently dominate the nasopharyngeal microbiome, ‘gatekeeping’ against respiratory pathogens by occupying niches and interacting with host immune cells,” the authors write. “Alterations in this community can therefore compromise mucosal defenses and increase susceptibility to infections.”

D pigrum and Corynebacterium are both commensals and, the researchers observed, they appear to have an interdependent relationship in the respiratory microbiome. “D. pigrum is likely dependent on Corynebacterium for nutrients and colonization support,” they write. “Such consortia may stabilize mucosal integrity, block pathogen overgrowth that worsens COVID-19–related lung damage, and/or reduces SARS-CoV-2 susceptibility through ACE2 [angiotensin-converting enzyme 2] downregulation and binding inhibition.”

Antibiotic use may affect the respiratory microbiome in two ways, hypothesize the researchers. First, antibiotic use may reduce the number of beneficial bacteria in the microbiome, making patients more susceptible to infection and increasing the risk of long COVID. Second, patients with initially lower levels of beneficial bacteria may be more prone to infections that require antibiotic use. 

Roughly 400 million people worldwide have long COVID

Long COVID remains a significant public health challenge. Research suggests that 6% of the world’s population, roughly 400 million people, will develop the condition. 

While the study has some limitations, including a modest sample size, the findings may help identify specific microbial signatures that serve as biomarkers for disease severity and even targets for intervention. “Early identification of patients at risk for PASC based on their nasopharyngeal microbial profiles could facilitate timely, personalized interventions aimed at restoring microbial balance and mitigating lung damage,” the researchers write.