Alterations in the respiratory tract microbiome in COVID-19: current observations and potential significance

Abstract

SARS-CoV-2 infection causes COVID-19 disease, which can result in consequences ranging from undetectable to fatal, focusing attention on the modulators of outcomes. The respiratory tract microbiome is thought to modulate the outcomes of infections such as influenza as well as acute lung injury, raising the question to what degree does the airway microbiome influence COVID-19? Here, we review the results of 56 studies examining COVID-19 and the respiratory tract microbiome, summarize the main generalizations, and point to useful avenues for further research. Although the results vary among studies, a few consistent findings stand out. The diversity of bacterial communities in the oropharynx typically declined with increasing disease severity. The relative abundance of Haemophilus and Neisseria also declined with severity. Multiple microbiome measures tracked with measures of systemic immune responses and COVID outcomes. For many of the conclusions drawn in these studies, the direction of causality is unknown-did an alteration in the microbiome result in increased COVID severity, did COVID severity alter the microbiome, or was some third factor the primary driver, such as medication use. Follow-up mechanistic studies can help answer these questions. Video Abstract.

Fig. 1

Associations of oropharyngeal microbiome features with COVID-19 relative to healthy controls. Analytical approaches and statistical methods varied among studies; results tabulated reflect the authors’ conclusions. Only studies that collected both COVID-19 and healthy controls are included; studies employing samples for either group from public data exclusively were not included. The sample size reports the number of COVID-19 patients and healthy controls. The results were filtered to emphasize findings consistent across more than one study

Fig. 2

Associations between oropharyngeal microbiome features and COVID-19 severity. Analytical approaches and statistical methods varied among studies; results tabulated reflect the authors’ conclusions. Disease severity comparisons varied and included asymptomatic vs symptomatic, moderate vs severe, alive vs dead, and others. The sample size refers to the number of COVID-19 patients only

Fig. 3

Associations of nasopharyngeal microbiome features with COVID-19, relative to healthy controls. Only studies that collected both COVID-19 and healthy controls are included; studies pulling samples for either group from public data exclusively were left out. The sample size reports the number of COVID-19 patients and healthy controls. The results were filtered to emphasize findings consistent across more than one study

Fig. 4

Associations between nasopharyngeal microbiome features and COVID-19 severity. Disease severity was defined differently across studies, ranging from asymptomatic vs symptomatic, to recovered vs deceased. Analytical approaches and statistical methods varied among studies; results tabulated reflect the authors’ conclusions. Disease severity comparisons varied, and included asymptomatic vs symptomatic, moderate vs severe, alive vs dead, and others. The sample size includes COVID-19 patients only