Incidence, case fatality and long-term outcomes in patients with sepsis - Nationwide registry studies of sepsis and COVID-19-related sepsis

Abstract

Sepsis is a severe immune reaction to an infection that leads to acute organ dysfunction and is a common cause of hospitalization, morbidity, and death. After surviving sepsis, many patients experience health impairments and reduced quality of life, which affects successful recovery, including the ability to return to work. Even though most studies have found an increasing incidence of sepsis in the last decade, a recent global study suggests the opposite. Epidemiological studies that describe trends are sparse, and it is essential to increase our knowledge of the incidence and prognosis of sepsis to plan for future health services. Therefore, this thesis aims a) to investigate the incidence and in-hospital mortality of sepsis, b) to investigate the prognosis of sepsis after hospital discharge, and c) to investigate the ability of sepsis survivors to return to work. Among 12,619,803 adult patients discharged from non-psychiatric hospitals in 2008-2021, 2.5% had a diagnostic code matching sepsis. This accounted for 317,705 hospitalizations with sepsis (Study 1), of which 222,282 (70%) were admitted with sepsis for the first time (Study 2). Further, of those admitted with a first sepsis episode, 12,260 (34%) were between 18 and 60 years old, working prior to hospitalization and discharged alive (Study 3). In Study 1, we found that the incidence of sepsis increased by 15% during the study period, mainly because of an increase in recurrent sepsis episodes. Patients over 60 years of age were more likely to be admitted with recurrent sepsis episodes. The mean in-hospital death was 13.7%. During the study period, the in-hospital mortality was reduced by 28%, and the highest reduction was among patients admitted with a first sepsis episode with 43%. Fewer sepsis patients were admitted during the first two COVID-19 pandemic years, and in-hospital mortality increased during this period. COVID-19-related sepsis accounted for 1 out of 10 hospitalizations with sepsis in this period. Compared to other sepsis patients, patients with COVID-19-related sepsis had a somewhat increased risk of in-hospital death. In Study 2, we found that 17%, 24%, 34%, and 59% of the patients did not survive 30 days, 90 days, 1 year, and 5 years, respectively. During the study period, we found a 14% reduction in 30-day, 90-day, and 1-year mortality and a 9% reduction in 5-year mortality. The highest decrease was seen among patients with respiratory tract infection as the cause of sepsis, with 10% reductions in 30-day and 90-day mortality and 16% and 11% reductions in 1-year and 5-year mortality. In addition, patients with comorbidities such as cancer, chronic lung disease, dementia, and chronic liver disease had an increased risk of dying compared to those with chronic heart and vascular disease. The mortality for patients in need of intensive care treatment compared to patients admitted to the ward was 26% vs. 17% at 30-day, 32% vs. 24% at 90-day, and 41% vs. 34% at 1-year. This difference aligned at 5-years and was 61% in patients that needed intensive care treatment and 58% in patients admitted to wards. Further, patients with COVID-19-related sepsis had approximately the same risk of death as other sepsis patients. In Study 3 (2010-2021), we found that 58% of sepsis patients had returned to work at ½ year, 68% at 1 year, and 63% at 2 years after hospitalization. The trends were stable during the study period (at ½ and 1 year), except at 2 years, where we found a 19% reduction in the proportion of patients that had returned to work between 2010 and 2019. Younger patients, patients with fewer comorbidities, and patients with fewer acute organ dysfunctions had an increased risk of returning to work. In addition, we found that patients discharged with COVID-19-related sepsis had an increased probability of returning to work compared to other sepsis patients. This thesis is based on individual-level data from 5 nationwide registries: The Norwegian Patient Registry (NPR), Statistic Norway (SSB), The Norwegian Cause of Death Registry (DÅR), The Norwegian Intensive Registry (NIR), and the Norwegian National Social Security System Registry (NAV). Diagnostic codes from NPR were used to identify sepsis in patients over 18 years of age hospitalized at all Norwegian public hospitals from 2008 through 2021. The extraction of diagnostic codes was in line with international standards and existed of one code with infection combined with a code of acute organ dysfunction, in addition to specific codes for sepsis. Patients‘ characteristics were retrieved from NPR, together with diagnostic codes for selected comorbidities. In Study 1, we used first and recurrent sepsis episodes from NPR and population data from SSB to calculate incidence and further the date of in-hospital death from NPR to calculate in-hospital mortality. In Study 2, we used the first sepsis episode from NPR and the death date from DÅR to estimate mortality. We linked the first sepsis episode from NPR to NIR in Study 2 and Study 3 to find patients needing intensive care treatment. Finally, to evaluate return to work in working-age patients discharged with a first sepsis episode in Study 3, we linked NPR with sick leave, work assessment, and disability data from NAV. Summarized, this thesis shows that the number of sepsis survivors increases. The decrease in the number of sepsis admissions during the COVID-19 pandemic, combined with increased in-hospital mortality, is concerning, and efforts to prevent the spread of severe acute respiratory syndrome-coronavirus (SARS-CoV-2) should be investigated further. The decreasing trend in patients working at 2 years is worrying. This and identifying vulnerable patient groups that warrant targeted interventions to improve long-term outcomes can be helpful knowledge for employers, politicians, and health leaders with responsibility for the future of health services.