SARS-CoV-2 infection predisposes patients to coinfection with
Staphylococcus aureus
Authors: Lubkin Ashira , Bernard-Raichon Lucie , DuMont Ashley L. , Valero Jimenez Ana Mayela , Putzel Gregory G. , Gago Juan , Zwack Erin E. , Olusanya Olufolakemi , Boguslawski Kristina M. , Dallari Simone , Dyzenhaus Sophie , Herrmann Christin , Ilmain Juliana K. , Isom Georgia L. , Pawline Miranda , Perault Andrew I. , Perelman Sofya , Sause William E. , Shahi Ifrah , St. John Amelia , Tierce Rebecca , Zheng Xuhui , Zhou Chunyi , Noval Maria G. , O'Keeffe Anna , Podkowik Magda , Gonzales Sandra , Inglima Kenneth , Desvignes Ludovic , Hochman Sarah E. , Stapleford Kenneth A. , Thorpe Lorna E. , Pironti Alejandro , Shopsin Bo , Cadwell Ken , Dittmann Meike , Torres Victor J. 
Published: July 2024

Severe COVID-19 has been associated with coinfections with bacterial and fungal pathogens. Notably, patients with COVID-19 who develop
Staphylococcus aureus
bacteremia exhibit higher rates of mortality than those infected with either pathogen alone. To understand this clinical scenario, we collected and examined
S. aureus
blood and respiratory isolates from a hospital in New York City during the early phase of the pandemic from both SARS-CoV-2+ and SARS-CoV-2− patients. Whole genome sequencing of these
S. aureus
isolates revealed broad phylogenetic diversity in both patient groups, suggesting that SARS-CoV-2 coinfection was not associated with a particular
S. aureus
lineage. Phenotypic characterization of the contemporary collection of
S. aureus
isolates from SARS-CoV-2+ and SARS-CoV-2− patients revealed no notable differences in several virulence traits examined. However, we noted a trend toward overrepresentation of
S. aureus
bloodstream strains with low cytotoxicity in the SARS-CoV-2+ group. We observed that patients coinfected with SARS-CoV-2 and
S. aureus
were more likely to die during the acute phase of infection when the coinfecting
S. aureus
strain exhibited high or low cytotoxicity. To further investigate the relationship between SARS-CoV-2 and
S. aureus
infections, we developed a murine coinfection model. These studies revealed that infection with SARS-CoV-2 renders mice susceptible to subsequent superinfection with low cytotoxicity
S. aureus
. Thus, SARS-CoV-2 infection sensitizes the host to coinfections, including
S. aureus
isolates with low intrinsic virulence.

IMPORTANCE

The COVID-19 pandemic has had an enormous impact on healthcare across the globe. Patients who were severely infected with SARS-CoV-2, the virus causing COVID-19, sometimes became infected with other pathogens, which is termed coinfection. If the coinfecting pathogen is the bacterium
Staphylococcus aureus
, there is an increased risk of patient death. We collected
S. aureus
strains that coinfected patients with SARS-CoV-2 to study the disease outcome caused by the interaction of these two important pathogens. We found that both in patients and in mice, coinfection with an
S. aureus
strain lacking toxicity resulted in more severe disease during the early phase of infection, compared with infection with either pathogen alone. Thus, SARS-CoV-2 infection can directly increase the severity of
S. aureus
infection.