In a recent study posted to the medRxiv* preprint server, researchers investigate the effect of colonization of the upper respiratory tract (URT) by Streptococcus pneumoniae on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vice versa in children and non-elderly adults in a household setting.
Herein, the researchers performed a longitudinal prospective observational study in households of the Netherlands where a member tested positive for the coronavirus disease 2019 (COVID-19) through reverse transcription-polymerase chain reaction (RT-PCR) assay three days before enrollment in the study. Two other household members also consented to participate in the study.
Study: Longitudinal dynamics of Streptococcus pneumoniae carriage and SARS-CoV-2 infection in households with children. Image Credit: Lotus_studio / Shutterstock.com
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Background
During the initial years of the COVID-19 pandemic, the incidence of invasive pneumococcal disease (IPD) due to Streptococcus pneumoniae declined substantially in multiple countries. Scientists believe that the large-scale implementation of non-pharmaceutical interventions (NPIs) limited pneumococcal transmission and IPD incidence throughout the pandemic.
However, some other studies have demonstrated that these declines were due to reduced circulation of seasonal respiratory viruses, rather than by reduced pneumococcal transmission.
Nevertheless, the interactions between certain respiratory viruses and Streptococcus pneumoniae appear to be synergistic. While the inflammation induced by Streptococcus pneumoniae in the URT facilitates infections by respiratory viruses, this reaction inhibits the innate immune response and prevents the URT microbiota from facilitating pneumococcal colonization, thereby increasing the risk of secondary pneumococcal pneumonia.
There is a scarcity of studies evaluating co-infections with SARS-CoV-2 and pneumococcus or viral-bacterial interactions. Furthermore, the longitudinal effects of the possible interference between these two pathogens within households with children and non-elderly adults under 65 years also remain largely unknown.
About the study
In the present study, researchers used quantitative molecular methods to detect Streptococcus pneumoniae and SARS-CoV-2 in self-collected saliva samples from the members of eight participating households between October 2020 and January 2021. This allowed for the characterization of longitudinal patterns of SARS-CoV-2 infection and pneumococcal carriage.
The study population comprised 197 adults younger than 65 year of age, as well as 118 children. Of these, 176 adults and 98 children provided ten self-collected saliva samples within 42 days of enrollment into this study.
Relative pneumococcal abundances were calculated by dividing pneumococcal abundances by overall bacterial abundances (16S), which were compared using a permutation test equivalent to the Mann-Whitney U test.
Next, the team used linear mixed-effects modeling to examine the correlation between SARS-CoV-2 infection, pneumococcal carriage status, and bacterial (16S) abundances, where individuals at the one-time point were classified as having low or high 16S abundance. A random intercept accounted for longitudinal intra- and inter-individual variance.
Time-dependent Cox proportional hazards models were used to evaluate the relationship between SARS-CoV-2 and pneumococcal carriage, abundance, and log-transformed overall bacterial (16S) abundance. For age-stratified hazard ratios (HR), two age groups including children under 18 years and adults over the age of 18, were considered.
Study findings
High carriage rates of Streptococcus pneumoniae remained relatively constant in Dutch households throughout the study period. This was likely due to the nationwide implementation of NPIs that reduced the circulation of seasonal respiratory viruses.
Although pneumococcal carriers appeared to be at a higher risk of SARS-CoV-2 infection and delayed viral clearance, the evidence was inadequate to show a strong impact of SARS-CoV-2 on pneumococcal carriage and abundance and vice versa.
Individuals with higher pneumococcal carriage and 16S abundances also had increased SARS-CoV-2 viral loads at multiple time points, thus suggesting their influence on COVID-19 progression. However, the variations in longitudinal viral load trajectories among these samples were insignificant, which was likely due to COVID-19-induced URT microbiome dysbiosis.
A previous study also described distinct URT microbiome composition profiles among hospitalized COVID-19 patients as compared to healthy individuals. Concerning relative pneumococcal abundances, no significant differences were observed between SARS-CoV-2 infected and uninfected individuals, nor was a marked shift in the serotype composition of all samples during the study duration observed.
Several studies documented that pneumococcal carriage rates in children were relatively unaffected during the COVID-19 pandemic. The cumulative HRs throughout this study were higher for children than adults at 2.14 and 0.83, respectively. This suggests that the relationship between pneumococcal abundances and SARS-CoV-2 infection was associated with children.
Conclusions
Taken together, the study observations suggest that SARS-CoV-2 infection did not appear to influence pneumococcal colonization, which is consistent with previous studies demonstrating that co-infections of SARS-CoV-2 and pneumococcus are uncommon.
However, pneumococcal carriers, especially children, were at an increased risk of contracting COVID-19. In addition, the study results suggested a correlation between high pneumococcal and 16S abundances and magnified viral loads, aside from delayed clearance of SARS-CoV-2 infection.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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