At the start of the COVID-19 pandemic, we did not know how SARS-CoV-2 would interact with other respiratory pathogens that typically circulate in our communities. In the following months, the circulation of these pathogens declined while invasive pneumococcal disease also declined worldwide. At that time, it was thought to be most likely due to non-pharmaceutical interventions to stop SARS-CoV-2 transmissions. The study “Detection of pneumococcus during hospitalization for SARS-CoV-2” in FEMS Microbes tested patients hospitalized with COVID-19 for co-infection with Streptococcus pneumoniae. Anne Stahlfeld and Anne Wyllie explain for the #FEMSmicroBlog what we can learn about the associations between pneumococcal and COVID-19 disease. #FascinatingMicrobes
Understanding the pneumococcal-SARS-CoV-2 co-infection
Streptococcus pneumoniae is a common commensal in the upper respiratory tract of individuals. Here, it can reside asymptomatically as part of our normal respiratory microbiome – in which case one speaks of pneumococcal colonization or carriage. Only if pneumococcus reaches a sterile site within the body, such as blood or cerebrospinal fluid, it can cause invasive pneumococcal disease.
However, infections with respiratory viruses, like influenza and respiratory syncytial virus (RSV), can disrupt such pneumococcal colonisation. This can then lead to infections of the lower respiratory tract often resulting in pneumonia.
From this bacteria-virus interaction, one can hypothesize that infection of the respiratory SARS-CoV-2 might also disrupt pneumococcal colonization. The subsequent co-infection might even lead to more severe outcomes.
The work “Detection of pneumococcus during hospitalization for SARS-CoV-2” in FEMS Microbes explores the possibility of this association. The study tested samples from a cohort of COVID-19 inpatients for the presence of pneumococcal carriage and lower respiratory tract infection. While saliva samples were tested by PCR to give conclusions about pneumococcal carriage, urine samples were tested by urinary antigen detection (UAD) to infer about respiratory tract infections.
The study found very little pneumococcal carriage as what would be expected for adults. However, it is likely that high rates of antibiotic use in this population impaired the ability to detect pneumococcal colonization. 65% of the inpatients included in this study received antibiotics during their hospital stay despite being admitted for COVID-19. This was further reflected by little bacterial growth when saliva was plated on blood plates in the laboratory – typically a full plate of bacteria should grow.
Moreover, while it was initially thought that non-pharmaceutical interventions, like mask-wearing and social distancing, might interrupt the community transmission of pneumococcus and thus explain the decreased rates of invasive pneumococcal disease. Other studies, however, conducted during the same period, demonstrated that pneumococcal carriage persisted during the pandemic at rates similar to pre-pandemic levels.
This was observed in children in Israel, Belgium and Serbia and by an extended study team in New Haven in community-dwelling of older adults and in asymptomatic healthcare workers. With this knowledge, it is now more likely that the lack of pneumococcal disease was due to the near absence of the other key respiratory viruses which generally circulate in the communities.
Potential reasons for severe COVID-19 symptoms
Interestingly, the study did not find an association between detecting S. pneumoniae in saliva by PCR and in urine by UAD. This means that those who tested positive for pneumococcal carriage by PCR were negative for UAD. Similarly, those who tested positive for UAD showed negative results in their saliva. However, a number of COVID-19 inpatients tested positive for S. pneumoniae in their urine samples implying that respiratory tract infections still occurred despite the lower rates of the invasive disease reported.
The study further observed an association between the presence of pneumococcus and more severe COVID-19 outcomes. Despite this, none of the patients in which pneumococcus was detected died during their hospital stay.
These findings may be confounded by the role of race-driven inequities, such as residential segregation and inadequate delivery of high-quality care. These factors can lead to increased exposure to pneumococcus and SARS-CoV-2 as well as increased severity of COVID-19 outcomes.
Overall, more data are needed to adequately address the association of pneumococcus and COVID-19 severity, including the role of racial inequity. The work suggests that future studies should explore this relationship in more depth and time with a particular focus on both pneumococcal carriage and the infection’s influence on COVID-19 outcomes.
- Read the article “Detection of pneumococcus during hospitalization for SARS-CoV-2” by Stahlfeld et al. (2022).
Anne Stahlfeld’s work centers around the intersection of epidemiology and health policy with a focus on the impact of infectious diseases on communities as well as capacity strengthening. During her MPH, Stahlfeld supported SARS-CoV-2 testing efforts including studying the use of pooled saliva for mass screening efforts, validating Dr. Wyllie’s Saliva Direct protocol for asymptomatic testing, and genomic surveillance in inpatients and outbreak settings. She currently works at Northwestern University to improve the modeling of within-host dynamics in relation to malaria transmission to address policy questions around the use of chemoprevention and other interventions to reach malaria control goals. In this role, she also helps running a faculty enrichment program for modelers from Sub-Saharan Africa to advance country-led modeling efforts.
Dr. Anne Wyllie’s work has identified saliva as a reliable sample type for the sensitive detection of Streptococcus pneumoniae (pneumococcus) in healthy older adults and more recently, of SARS-CoV-2 in persons suspected of COVID-19. Wyllie validated and optimized saliva for SARS-CoV-2 detection and developed SalivaDirect: a simple, scalable and importantly, cost-effective method to help alleviate SARS-CoV-2 testing demands. Wyllie’s SalivaDirect Initiative at the Yale School of Public Health remains devoted to providing public health guidance, advancing saliva diagnostics and enabling the safe re-opening of communities worldwide.
About this blog section
The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.
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