SARS-CoV-2-Associated Sepsis More Common, Deadly During the Early Pandemic


Study is the first to compare SARS-CoV-2–associated sepsis and presumed bacterial sepsis on mortality and incidence.

Sepsis associated with SARS-CoV-2 infection was more deadly than presumed bacterial sepsis during the early period of the COVID-19 pandemic, according to new research published in JAMA Open Network. However, the number of SARS-CoV-2-associated sepsis cases decreased from the beginning of the pandemic to November 2022—as did the in-hospital mortality rate—while the mortality rate of bacterial sepsis remained the same.

Image credit: Dr_Microbe |

Image credit: Dr_Microbe |

“SARS-CoV-2 accounted for approximately 1 in 6 cases of sepsis during the first 33 months of the COVID-19 pandemic,” the study authors wrote in the article.

The authors said this is the first review comparing SARS-CoV-2–associated sepsis and presumed bacterial sepsis on mortality and incidence. The findings suggest that SARS-CoV-2 caused a more significant burden on hospitalized patients during the pandemic, according to the study.

Sepsis is defined as fatal organ disfunction that occurs when the body has a dysregulated response to an infection. While typically associated with bacterial infection, the COVID-19 pandemic showed that viral infection can contribute to the occurrence of sepsis and associated mortality, although previous studies are limited.

Investigators conducted the retrospective cohort study to understand the difference between SARS-CoV-2–associated sepsis and presumed bacterial sepsis on frequency and mortality outcomes during the COVID-19 pandemic. The authors defined SARS-CoV-2–associated sepsis as having a positive SARS-CoV-2 polymerase chain reaction test and concurrent organ dysfunction such as vasopressors. The criterion for presumed bacterial sepsis is modified from US Centers for Disease Control and Prevention criteria for an adult sepsis event.

Between March 2020 and November 2022, data on 261,595 patients (431,017 hospital encounters total) at 5 Massachusetts hospitals were collected and evaluated using negative binomial and logistic regression models. The team identified the proportion of hospitalizations (quarterly incidence) and hospital mortality associated with each disease.

Among 23,276 patients with SARS-CoV-2 infection, 6558 contracted SARS-CoV-2-associated sepsis confirmed using electronic health record (EHR)–based algorithms for SARS-CoV-2–associated sepsis criteria. Among patients who did not have SARS-CoV-2 infection, 30,604 patients hadpresumed bacterial sepsis.

Among patients admitted to the hospital with SARS-CoV-2 infection, 28.2% had SARS-CoV–2 associated sepsis. However, only 1.5% of all hospital admissions were due to SARS-CoV–2 associated sepsis, while 7.1% of hospitalizations were caused by bacterial sepsis.

Although a larger number of hospital admissions can be attributed to bacterial sepsis, the in-hospital mortality for SARS-CoV-2–associated sepsis was higher during the first 10 quarters of the COVID-19 pandemic at 33.4%. The in-hospital mortality rate for bacterial sepsis was 14.5% at the beginning of the pandemic, but it remained stable throughout the study period.

Although the mortality rate of bacterial sepsis appears consistent throughout the study, the in-hospital mortality rate of SARS-CoV-2–associated sepsis decreased with time, dropping from 33.4% to 14.9% by November 2022.

“[This] likely reflects a combination of increased immunity from vaccines and prior infections, advances in patient management (antivirals, immunomodulators, increased use of non-invasive respiratory support), and less severe strains on hospital capacity,” the study authors wrote.

Study limitations included the use of a single health system. In addition, HER-based approach to capturing sepsis cases is imperfect, misattributing organ disfunction to SARS-CoV-2 infection, and confounding, according to the investigators.

The authors concluded, “Our findings may help increase awareness of the underrecognized contribution of viral pathogens to sepsis and to improve nuance in our approach to sepsis diagnosis and treatment.”


Shappell CN, Klompas M, Chan C, et al. Use of Electronic Clinical Data to Track Incidence and Mortality for SARS-CoV-2–Associated Sepsis. JAMA Netw Open. 2023;6(9):e2335728. DOI:10.1001/jamanetworkopen.2023.35728

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