What is the association of pneumococcal carriage with SARS-CoV-2 infection?

By Dr. Chinta SidharthanOct 12 2022Reviewed by Danielle Ellis, B.Sc.

In a recent study posted to the medRxiv* preprint server, a team of researchers explored the association between Streptococcus pneumoniae and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the upper respiratory tracts of coronavirus disease 2019 (COVID-19) positive individuals.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

Streptococcus pneumoniae has been associated with various respiratory disease viruses, such as the influenza virus, respiratory syncytial virus, and human rhinoviruses in the upper airways. Pneumococcal infections have commonly been observed after many viral respiratory diseases.

The presence of pneumococci has also been detected in the early stages of viral infections. Epidemiological studies and experiments on animal models have indicated an increased risk of influenza and other respiratory viral infections associated with pneumococcal carriage.

Studies in the UK found a three-fold increase in the likelihood of pneumococcal presence in the saliva of COVID-19 patients. Concurrent SARS-CoV-2 infections with invasive pneumococcal disease (IPD) were also associated with increased mortality. A study in the United States (US) also found that the 13-valent pneumococcal conjugate vaccine decreased the severity of COVID-19. However, the interactions between pneumococcal carriage and the severity of SARS-CoV-2 infections need to be explored further.

About the study

In the present study, the team collected saliva samples between 16 July and 30 November 2020, from non-pregnant adults in Monterey County, California, aged 18 years or older. The samples were acquired during SARS-CoV-2 testing at outpatient clinics and mobile community outreach venues.

Quantitative polymerase chain reaction (qPCR) amplification of the major autolysin gene (lytA) and permease gene of the pia ABC transporter (piaB) was used to determine pneumococcal carriage. Samples were considered pneumococci positive if the cycle threshold values were less than 40 or 35 for a more stringent classification.

Transcription-mediated amplification (TMA) assay of oropharyngeal swabs was used to confirm SARS-CoV-2 infections. Cycle threshold values from qPCR assays of SARS-CoV-2 structural envelope protein (E) and nucleocapsid (N) genes were used to determine viral abundance.

The adjusted odds ratios were calculated based on factors such as age, body mass index, sex, smoking behavior, the community of residence, household annual income, and potential COVID-19 risk behaviors such as contact with confirmed COVID-19 patients, not wearing masks, and attending large indoor gatherings. 

Results

The results reported evidence of interactions between SARS-CoV-2 infections and pneumococcal carriage. Individuals experiencing severe COVID-19 symptoms showed stronger associations with pneumococcal carriage.

The study included 564 participants from outpatient clinics and 714 from mobile outreach facilities. Pneumococci were detected in 9.2% of participants across the two groups, and SARS-CoV-2 infections were detected in 27.4% of these pneumococcal carriers. In comparison, only 9.6% of the non-carriers had SARS-CoV-2 infections.

A decrease in every cycle in the cycle threshold value for piaB increased the odds of SARS-CoV-2 infection, suggesting a density-dependent association between pneumococcal presence and COVID-19 risk. Furthermore, pneumococcal carriers had a two-fold higher probability of contracting SARS-CoV-2 infection from exposure to a symptomatic individual than non-carriers of pneumococci.

Evidence suggested that colonization by Streptococcus pneumoniae preceded the exposure to SARS-CoV-2 for most participants. The authors presented two possible explanations for the finding. The nasopharyngeal inflammation caused by pneumococcal growth could have increased the risk of SARS-CoV-2 infections. Alternately, the higher pneumococcal density could result from a recent SARS-CoV-2 infection. 

The authors discussed some of the limitations of the study. Firstly, since the participants were largely farmworkers from low-income communities, the results can not be generalized to the rest of the population. Furthermore, social interactions and factors such as participants living or working together were not considered, and it could influence exposure assessments.

Since the study was conducted in 2020, it did not include participants infected with the newer SARS-CoV-2 variants. Moreover, the recruitment of participants from outpatient and mobile outreach clinics excluded participants who were hospitalized with severe COVID-19 manifestations. Therefore, the association between pneumococcal carriage and severe COVID-19 outcomes was not studied comprehensively.

Conclusions

To summarize, the study investigated associations between Streptococcus pneumoniae colonization of upper respiratory tracts and SARS-CoV-2 infections among participants from California consisting mostly of farm workers.

The results indicated a positive, density-dependent association between pneumococcal carriage and concurrent SARS-CoV-2 infections. Furthermore, pneumococcal carriers had twice the risk of contracting a SARS-CoV-2 infection from exposure to a symptomatic patient than individuals without pneumococci in their upper airways.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources