Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study

Xiaomin Zhong, Diane Ashiru-Oredope, Alexander Pate, Glen P. Martin, Anita Sharma, Paul Dark, Tim Felton, Claire Lake, Brian MacKenna, Amir Mehrkar, Sebastian C.J. Bacon, Jon Massey, Peter Inglesby, Ben Goldacre, Kieran Hand, Sian Bladon, Neil Cunningham, Ellie Gilham, Colin S. Brown, Mariyam MirfendereskyAlex J. Walker, Brian MacKenna, Peter Inglesby, Ben Goldacre, Helen J. Curtis, Jessica Morley, Amir Mehrkar, Sebastian C.J. Bacon, George Hickman, Richard Croker, David Evans, Tom Ward, Nicholas J. DeVito, Louis Fisher, Amelia C.A. Green, Jon Massey, Rebecca M. Smith, William J. Hulme, Simon Davy, Colm D. Andrews, Lisa E.M. Hopcroft, Iain Dillingham, Rose Higgins, Christine Cunningham, Milan Wiedemann, Linda Nab, Steven Maude, Orla Macdonald, Ben F.C. Butler-Cole, Thomas O'Dwyer, Catherine L. Stables, Christopher Wood, Andrew D. Brown, Victoria Speed, Lucy Bridges, Andrea L. Schaffer, Caroline E. Walters, Christopher Bates, Jonathan Cockburn, John Parry, Frank Hester, Sam Harper, Victoria Palin, Tjeerd Pieter van Staa

Research output: Contribution to journalArticlepeer-review


Background: Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality. Methods: With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality. Findings: The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77–1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35–3.73]), chronic liver disease (adjusted OR 3.08 [2.97–3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55–2.70], stage 5: adjusted OR 6.23 [5.81–6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods. Interpretation: Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients. Funding: The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.

Original languageEnglish
Article number102321
Early online date23 Nov 2023
Publication statusPublished - 1 Dec 2023


  • COVID-19 pandemic
  • Deprivation
  • Health inequality
  • Morbidity
  • Primary care
  • Sepsis


Dive into the research topics of 'Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study'. Together they form a unique fingerprint.

Cite this