Prevalence, Clinical Characteristics, and Outcomes of Sepsis Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Versus Other Pathogens in Hospitalized Patients With COVID-19

Abstract

IMPORTANCE:The prevalence and causes of sepsis in patients hospitalized with COVID-19 are poorly characterized. OBJECTIVES:To investigate the prevalence, clinical characteristics, and outcomes of sepsis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) versus other pathogens in patients hospitalized with COVID-19. DESIGN, SETTING, AND PARTICIPANTS:Cross-sectional, retrospective chart review of 200 randomly selected patients hospitalized with COVID-19 at four Massachusetts hospitals between March 2020 and March 2021. MAIN OUTCOMES AND MEASURES:The presence or absence of sepsis was determined per Sepsis-3 criteria (infection leading to an increase in Sequential Organ Failure Assessment score by ≥ 2 points above baseline). Sepsis episodes were assessed as caused by SARS-CoV-2, other pathogens, or both. Rates of organ dysfunction and in-hospital death were also assessed. RESULTS:Sepsis was present in 65 of 200 COVID-19 hospitalizations (32.5%), of which 46 of 65 sepsis episodes (70.8%) were due to SARS-CoV-2 alone, 17 of 65 (26.2%) were due to both SARS-CoV-2 and non-SARS-CoV-2 infections, and two of 65 (3.1%) were due to bacterial infection alone. SARS-CoV-2-related organ dysfunction in patients with sepsis occurred a median of 1 day after admission (interquartile range, 0-2 d) and most often presented as respiratory (93.7%), neurologic (46.0%), and/or renal (39.7%) dysfunctions. In-hospital death occurred in 28 of 200 COVID-19 hospitalizations (14.0%), including two of 135 patients without sepsis (1.5%), 16 of 46 patients with sepsis (34.8%) due to SARS-CoV-2 alone, and 10 of 17 patients with sepsis (58.8%) due to both SARS-CoV-2 and bacterial pathogens. CONCLUSIONS:Sepsis occurred in one in three patients hospitalized with COVID-19 and was primarily caused by SARS-CoV-2 itself, although bacterial infection also contributed in a quarter of sepsis cases. Mortality in COVID-19 patients with sepsis was high, especially in patients with mixed SARS-CoV-2 and bacterial sepsis. These findings affirm SARS-CoV-2 as an important cause of sepsis and highlight the need to improve surveillance, recognition, prevention, and treatment of both viral and bacterial sepsis in hospitalized patients with COVID-19.

Use of Electronic Clinical Data to Track Incidence and Mortality for SARS-CoV-2–Associated Sepsis

“…between estimates of SARS-CoV-2-associated sepsis incidence using our EHR-based approach and previous approaches using medical record reviews and pooled organ dysfunctions provides further support for its validity. 17 In-hospital mortality was higher for SARS-CoV-2-associated sepsis vs presumed bacterial sepsis during the first 10 quarters of the COVID-19 pandemic but decreased over time. This finding emphasizes the potential of respiratory viruses to trigger severe, life-threatening disease and underscores the peril of our relative lack of effective antiviral therapeutics for most respiratory viruses.…”

“…[12][13][14][15][16] Previous investigations specifically assessing the prevalence and outcomes for SARS-CoV-2-associated sepsis have been limited by small sample sizes, single center design, and/or heterogeneous definitions of organ dysfunction, and were conducted using data from early in the COVID-19 pandemic. 17,18 Electronic health record (EHR)-based surveillance using clinical markers of concurrent infection and organ dysfunction is rapidly becoming the state-of-the-art method for widescale sepsis surveillance. 10,19 This strategy allows for more objective and reproducible analyses across hospitals and has been used by the US Centers for Disease Control and Prevention (CDC) to quantify the national burden of sepsis.…”

A National Perspective on the Impact of the COVID-19 Pandemic on Heart Failure Hospitalizations in the United States

“…A COVID-19 infection has also been found to manifest a primary septic shock event in upwards of 70.8% of total septic episodes in a cohort by Shappell et al , thereby underscoring the need for vigilance in infected patients 33 . Subsequently, a con-current COVID-19 infection almost doubles the incidence of mortality among those experiencing septic shock, regardless of cause 34 .…”

Role of miRNA dysregulation in sepsis

“…As an example, surviving sepsis guidelines have been written specifically for COVID-19 (Alhazzani et al 2021), yet have a high degree of overlap for managing sepsis in general. Published reports refer to patients with "sepsis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)" (Shappell et al 2022), while others underline the differences between the two diseases (Klaz 2021). At the very least, the two conditions have many parallels at the clinical as well as molecular level suggesting a similar underlying pathogenesis (Olwal et al 2021;Baghela et al 2022).…”