Bacterial co-infection is a major risk factor for death, intensive care unit admission and mechanical ventilation, according to a multi-center, retrospective cohort study published in the journal Critical Care and led by University of Alabama at Birmingham researchers.

Coronavirus disease 2019, or COVID-19, has killed more than 6.3 million people worldwide.

This recent study of 13,781 COVID-19 inpatient encounters from 2020 to 2022 found that bacterial co-infection in the blood, known as bacteremia, is a greater risk factor for death, intensive care unit admission and mechanical ventilation than previously described risk factors for COVID-19 severity and mortality, such as advanced age, male sex or various comorbidities.

The study reviewed COVID-19 inpatient encounters at UAB Hospital and at Ochsner Louisiana State University Health Shreveport hospitals and divided them into three groups: confirmed bacterial co-infection, as measured by a blood test at 48 hours after admission; suspected bacterial co-infection in patients receiving antimicrobials; and no bacterial co-infection.

Bacterial co-infection is a known major source of sickness and death in the context of other respiratory viral infections such as influenza, parainfluenza or RSV. However, it has been unclear regarding the frequency of bacteremic co-infection in COVID-19 and the impact it has on clinical outcomes.

“Although confirmed bacteremic co-infections are rare in COVID-19, less than 4 percent of inpatient admissions, our results show that COVID-19 patients with these co-infections have a staggering 25 percent risk of death at 30 days in UAB patients and a similar risk of 20 percent at Ochsner Louisiana State University Health Shreveport, or OLHS,” said Amit Gaggar, M.D., Ph.D., UAB Department of MedicineDivision of Pulmonary, Allergy and Critical Care Medicine. Gaggar, in collaboration with the Hugh Kaul Precision Medicine Institute director, Matthew Might, Ph.D., and infectious disease physician-scientist Nathaniel Erdmann, M.D., Ph.D., co-led the study.

“These results strongly suggest an underappreciated interaction between bacterial pathogens and the COVID-19 virus, SARS-CoV-2, and their impact on clinical outcomes,” co-senior author Erdmann added.

Matthew Might
Photography: Steve WoodSpecifically, the researchers found that the in-hospital mortality for COVID-19 co-infections of 26 percent at UAB and 22 percent at OLHS exceeded that of the suspected co-infection (UAB, 24 percent; OLHS, 12 percent) and the no co-infection groups (UAB, 5.9 percent; OLHS, 5.1 percent). Furthermore, a control group of 1,703 UAB inpatients with community-acquired bacteremias during a period before the COVID-19 pandemic had a 5.9 percent in-hospital mortality rate. 

The researchers also identified laboratory trends associated with COVID-19 bacterial co-infection — a neutrophil-to-lymphocyte ratio of 15 or greater, and the Systemic Inflammatory Response Syndrome, or SIRS, criteria of abnormal white blood cell counts or a heart rate greater than 90 beats per minute. These can help health care providers discriminate COVID-19 bacterial co-infections within 24 hours of admission.

“These results emphasize the role of bacteria in SARS-CoV-2 mortality, and highlight the potential for neutrophil-to-lymphocyte ratio as a rapid and easily available prognostic biomarker of bacterial coinfection and, relatedly, disease severity,” said co-senior author Might.

Strengths of this study were the two large, demographically diverse, independent cohorts — UAB reflects an academic hospital and Level I trauma center serving five surrounding states, and OLHS includes encounters from rural, suburban and academic medical centers across the state of Louisiana. Both cohorts overall were well matched for patient age, race, sex and inpatient length of stay.

“One of the novel opportunities of the COVID-19 pandemic has been the seismic shift in collected and searchable data captured by electronic medical record, or EMR, systems. This resource, in combination with the collaborative spirit of experts from UAB and OLHS, provides the bedrock for biomedical informatic studies that can produce clinically useful observations for the betterment of patients,” said primary and corresponding author of the study Michael John Patton, an aspiring clinician and biomedical informatician in UAB’s Medical Scientist Training Program for M.D.-Ph.D. trainees.  

Nathaniel Erdmann
Photography: Lexi CoonCo-authors with Gaggar, Might, Erdmann and Patton are Carlos J. Orihuela, UAB Department of Microbiology; Kevin S. Harrod, UAB Department of Anesthesiology and Perioperative Medicine; Mohammad A.N. Bhuiyan and Christopher G. Kevil, Louisiana State University Health Sciences Center at Shreveport; Paari Dominic, Department of Medicine, University of Iowa, Iowa City; Daniel Fort, Ochsner Health System, New Orleans, Louisiana; Vincent X. Liu, Kaiser Permanente Division of Research, Oakland, California; Maha Farhat, Harvard University Medical School, Boston, Massachusetts; Jonathan L. Koff, Department of Medicine, Yale University, New Haven, Connecticut; Charitharth V. Lal, UAB Department of Pediatrics, Neonatology Division; Anuj Gaggar, ArriveBio, San Francisco, California; and Robert P. Richter, UAB Department of Pediatrics, Division of Pediatric Critical Care.

Erdmann is in the UAB Department of Medicine, Division of Infectious Diseases, and Might is in the UAB Department of Medicine. 

Support came from National Institutes of Health grants GM121307, GM121307-05S1, AI156898, AI129705, HL153113, OTA-21-015E, HL149944 and GM144788; American Lung Association grant COVID-862668; Cystic Fibrosis Foundation grant HARROD20G0; Veterans Administration Merit Award I01CX001969-01A2; and the COVID-19 Urgent Research Response Fund established by the Hugh Kaul Precision Medicine Network at UAB.

At UAB, Medicine, Microbiology, Anesthesiology and Perioperative Medicine, and Pediatrics are departments in the Marnix E. Heersink School of Medicine.