Long-term mortality following SARS-CoV-2 infection: A national cohort study from Estonia

Abstract

Background: The objective of this study was to describe 12-month mortality following SARS-CoV-2 infection compared with a reference population with no history of SARS-CoV-2.

Methods: Nationwide cohort study using electronic health care data on SARS-CoV-2 RNA positive cases (n= 66,287) and reference group subjects (n=254,969) with linkage to SARS-CoV-2 testing and death records.

Findings: People infected with SARS-COV-2 had more than three times the risk of dying over the following year compared with those who remained uninfected (aHR 3·1, 95%CI 2·9-3·3). Short-term mortality (up to 5 weeks post-infection) was significantly higher among COVID-19 group (1623·0/10 000) than in the reference group (118/10 000). For COVID-19 cases aged 60 years or older, increased mortality persisted until the end of the first year after infection, and was related to increased risk for cardiovascular (aHR 2·1, 95%CI 1·8-2·3), cancer (aHR 1·5, 95%CI 1·2-1·9), respiratory system diseases (aHR 1·9, 95%CI 1·2-3·0), and other causes of death (aHR 1·8, 95%CI 1·4-2·2).

Interpretation: Increased risk of death from SARS-CoV-2 is not limited to the acute illness: SARS-CoV-2 infection carries a substantially increased mortality in the following 12 months. This excess death mainly occurs in older people and is driven by broad array of causes of death.

Funding: Research was carried out with the support of Estonian Research Council (grants PRG1197, PRG198), European Regional Development Fund (RITA 1/02-120) and European Social Fund via IT Academy program.

Keywords: COVID-19; Cardiovascular death; Estonia; Mortality; Population-based; SARS-CoV-2.

Figure 1

Cumulative probability of dying by group status: SARS-CoV-2 cases (all (A) and by disease severity (B)) and reference group, one year post- SARS-CoV-2 infection period, Estonia 2020-2021.

Figure 2

Cumulative probability of dying by age group among SARS-CoV-2 cases and reference group by the period of observation (early, mid- and long-term post-acute SARS-CoV-2 infection), Estonia 2020-2021. (A) SARS-CoV-2 cases compared to reference group (among those 60 years and older); (B) SARS-CoV-2 cases compared to reference group (among those less than 60 years old).

Figure 3

Time-varying hazard ratios for death from any cause among SARS-CoV-2 cases compared to reference group (early, mid- and long-term post-acute SARS-CoV-2 infection), Estonia 2020-2021. (A) SARS-CoV-2 cases compared to reference group (among those 60 years and older); (B) SARS-CoV-2 cases compared to reference group (among those less than 60 years old).

Figure 4

Competing risk analysis for cause-specific mortality of SARS-CoV-2 cases and in the reference group, Estonia 2020-2021. (A) SARS-CoV-2 cases compared to reference group (among those 60 years and older); (B) SARS-CoV-2 cases compared to reference group (among those less than 60 years old).