Changes in the characteristics and outcomes of COVID-19 patients from the early pandemic to the delta variant epidemic: a nationwide population-based study

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed because of virus mutations, vaccine dissemination, treatment development and policies, among other factors. These factors have a dynamic and complex effect on the characteristics and outcomes of patients. Therefore, there is an urgent need to understand those changes and update the evidence. We used a large-scale real-world data set of 937,758 patients with COVID-19 from a nationwide claims database that included outpatients and inpatients in Japan to investigate the changes in their characteristics, outcomes and risk factors for severity/mortality from the early pandemic to the delta variant-predominant waves. The severity of COVID-19 was defined according to the modified World Health Organization clinical-progression ordinal scale. With changing waves, mean patient age decreased, and proportion of patients with comorbidities decreased. The incidences of "severe COVID-19 or death (i.e. ≥severe COVID-19)" and "death" markedly declined (5.0% and 2.9%, wild-type-predominant; 4.6% and 2.2%, alpha variant-predominant and 1.4% and 0.4%, delta variant-predominant waves, respectively). Across the wave shift, risk factors for ≥ severe COVID-19 and death, including older age, male, malignancy, congestive heart failure and chronic obstructive pulmonary disease, were largely consistent. The significance of some factors, such as liver disease, varied as per the wave. This study, one of the largest population-based studies on COVID-19, showed that patient characteristics and outcomes changed during the waves. Risk factors for severity/mortality were similar across all waves, but some factors were inconsistent. These data suggest that the clinical status of COVID-19 will change further with the coming epidemic wave.

Keywords: COVID-19; NDB; epidemiology; national database of health insurance claims and specific health checkups of Japan; risk factors.

Figure 1.

Incidences of ≥ severe COVID-19 and of death by wave. During the wild-type-, alpha – and delta-predominant waves, the incidence of ≥ severe COVID-19 ^a was 5.0%, 4.5% and 1.4%, respectively. During the wild-type-, alpha – and delta-predominant waves, the incidence of death was 2.9%, 2.2% and 0.4%, respectively. ^a Based on the total number of patients with an outcome of severe COVID-19 or death.

Figure 2.

Incidences of ≥ severe COVID-19 and of death by age group and waves. During the wild-type-, alpha – and delta-predominant waves, the incidence of ≥ severe COVID-19 ^a was 0.4%, 0.7% and 0.5%, respectively, in the 20–49 years age group; 3.2%, 4.6% and 3.0%, respectively, in the 50–64 years age group; 10.6%, 10.8% and 5.4% respectively, in the 65–79 years age group and 18.9%, 19.3% and 11.3%, respectively, in the ≥80 years age group. During the wild-type-, alpha – and delta-predominant waves, the incidence of death was 0.07%, 0.06% and 0.04%, respectively, in the 20–49 years age group; 0.6%, 0.6% and 0.4%, respectively, in the 50–64 years age group; 4.9%, 4.4% and 2.8%, respectively, in the 65–79 years age group; and 16.0%, 16.0% and 9.7%, respectively, in the ≥80 years age group. ^a Based on the total number of patients with an outcome of severe COVID-19 or death.

Figure 3.

Multivariable logistic regression analyses for ≥ severe COVID-19 and for death by wave. Adjusted odds ratios and 95% confidence intervals were plotted. The odds ratios were adjusted for age, sex and comorbidities. Wild-type-predominant; 1 January 2020–18 April 2021, alpha-predominant; 19 April 2021–18 July 2021, delta-predominant; 19 July 2021–31 August 2021. COPD, chronic obstructive pulmonary disease.