SARS-CoV-2 infection predisposes patients to coinfection with Staphylococcus aureus
Ashira Lubkin,
Lucie Bernard-Raichon,
Ashley L. DuMont,
Ana Mayela Valero Jimenez,
Gregory G. Putzel,
Juan Gago,
Erin E. Zwack,
Olufolakemi Olusanya,
Kristina M. Boguslawski,
Simone Dallari,
Sophie Dyzenhaus,
Christin Herrmann,
Juliana K. Ilmain,
Georgia L. Isom,
Miranda Pawline,
Andrew I. Perault,
Sofya Perelman,
William E. Sause,
Ifrah Shahi,
Amelia St. John,
Rebecca Tierce,
Xuhui Zheng,
Chunyi Zhou,
Maria G. Noval,
Anna O'Keeffe,
Magda Podkowik,
Sandra Gonzales,
Kenneth Inglima,
Ludovic Desvignes,
Sarah E. Hochman,
Kenneth A. Stapleford,
Lorna E. Thorpe,
Alejandro Pironti,
Bo Shopsin,
Ken Cadwell,
Meike Dittmann,
Victor J. Torres
Affiliations
Ashira Lubkin
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Lucie Bernard-Raichon
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Ashley L. DuMont
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Ana Mayela Valero Jimenez
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Gregory G. Putzel
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Juan Gago
Department of Population Health, New York University Grossman School of Medicine, New York, New York, USA
Erin E. Zwack
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Olufolakemi Olusanya
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Kristina M. Boguslawski
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Simone Dallari
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Sophie Dyzenhaus
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Christin Herrmann
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Juliana K. Ilmain
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Georgia L. Isom
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Miranda Pawline
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Andrew I. Perault
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Sofya Perelman
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
William E. Sause
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Ifrah Shahi
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Amelia St. John
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Rebecca Tierce
Division of Comparative Medicine, New York University Langone Health, New York, New York, USA
Xuhui Zheng
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Chunyi Zhou
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Maria G. Noval
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Anna O'Keeffe
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Magda Podkowik
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Sandra Gonzales
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Kenneth Inglima
Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA
Ludovic Desvignes
Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA
Sarah E. Hochman
Antimicrobial-Resistant Pathogens Program, Microbial Genomics Core Lab, New York University Langone Health, New York, New York, USA
Kenneth A. Stapleford
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Lorna E. Thorpe
Department of Population Health, New York University Grossman School of Medicine, New York, New York, USA
Alejandro Pironti
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Bo Shopsin
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Ken Cadwell
Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
Meike Dittmann
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
Victor J. Torres
Department of Microbiology, New York University Grossman School of Medicine, New York, New York, USA
ABSTRACT 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.IMPORTANCEThe 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.
