Clinical and demographic inequalities in COVID-19-associated mortality

In a recent study posted to the medRxiv* preprint server, researchers quantified the relative and absolute changes in coronavirus disease 2019 (COVID-19)-related mortality based on clinical and demographical profiles of 18 million adult patients throughout the pandemic in England.

Studies have reported a disproportionate impact of the COVID-19 pandemic varying by patient demographics and clinical subgroups. Previous studies in the United Kingdom (UK) have reported more COVID-19 -associated deaths in the first wave in male, non-White and elder persons with public-facing jobs, residing in multi-generation households, and having learning disabilities, and comorbidities such as kidney disorders and obesity.

The rates associated with the second and third waves have been much lower, possibly due to widespread COVID-19 vaccinations and improved management of COVID-19. However, the clinical and demographical inequalities in COVID-19-associated deaths may persist over time.

About the study

In the present observational study, researchers reported the trends in COVID-19-associated mortality across demographical and clinical subgroups of patients over the successive waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic between February 2020 and December 2021, for the National Health Service (NHS) England.

Primary care data of individuals registered with general practitioners (GP) and mortality registry data of the three initial waves of the COVID-19 pandemic in England were obtained from the OpenSAFELY-TPP database (first wave: 23 March to 30 May 2020; second wave: 7 September 2020 to 24 April 2021; and third wave: 28 May to 14 December 2021).

The study population included 18.7 million, 18.8 million, and 19 million adult patients infected with SARS-CoV-2 in the first, second and third waves, respectively. Individuals were excluded if data on their sex and demographics, such as the IMD (index of multiple deprivations) values or STP (sustainability and transformation partnership) regions, were missing.

The main study outcome was COVID-19-associated deaths based on the linked mortality registry records obtained from the ONS (office for national statistics). Covariates considered for the analysis were sex, age, race, smoking habits, IMD values, STP regions of patient GPs and body mass index (BMI). The comorbidities considered were hypertension, diabetes, asthma and other chronic respiratory disorders, chronic cardiovascular disorders, hematological and non-hematological cancers, chronic kidney diseases with/without kidney replacement, dialysis or kidney transplantation.

In addition, comorbidities included chronic hepatic diseases, neurological diseases, organ transplantation, asplenia, lupus/psoriasis/rheumatoid arthritis, learning disabilities, severe mental disorders, and conditions causing immunosuppression. Cox proportional models were used for the analysis, and the crude COVID-19-associated mortality rates for every 1,000 individual years were calculated in relative and absolute terms.

Results

The crude absolute COVID-19-associated mortality rate reduced from 4.5 in the first wave to 2.7 in the second wave and further to 0.6 in the third wave. The absolute mortality rates were reduced by 90% and 20% between the first and third waves among patients above 80 years of age and among patients aged between 18 years and 39 years.

The greater proportional decrease in sex- and age-standardized COVID-19-associated mortality was also observed among patients with severe mental disorders, neurological diseases and learning disabilities. On the contrary, standardized mortality rates among recipients of organ transplants were largely constant across the three waves of the pandemic (10 deaths for every 1,000 individual-years).

In addition, a minor reduction in mortality rates across successive waves was observed among persons with renal diseases, obesity, hematological cancers and immunosuppressive conditions (0.2-0.5-fold changes for the third wave vs the first wave).  As a consequence, the relative hazards of COVID-19-associated deaths reduced with time for variables such as age, were constant for variables such as race and sex and elevated for variables such as kidney diseases, obesity, hematological cancers, immunosuppressive conditions, and organ transplantations.

The relative hazard of deaths for individuals aged ≥80 years vs. those aged 50 to 59 years were 41.6, 36.5 and 15.3 for the first, second and third waves, respectively, with a 0.4-fold-change for the third wave vs. the first wave. The relative hazard of death for individuals with vs. without learning disabilities were 8.7, 6.9, and 3.9 in the first, second and third waves, respectively, with a 0.5-fold change for the third wave vs. the first wave.

The relative hazards of death for men vs. women were 1.7, 1.6 and 1.9 in the first, second and third waves, respectively. The relative hazards of death for Asians vs Whites were 1.5, 2.0 and 1.9 in the first, second and third waves, respectively. The relative hazards of death for the most deprived (IMD 1) vs the least deprived (IMD 5), were 2.2, 2.2 and 2.8 in the first, second and third waves, respectively.

Overall, the study findings showed that COVID-19-associated mortality reduced over succeeding waves of the COVID-19 pandemic, especially among elders and individuals with neurological diseases, severe mental disorders, and learning disabilities. However, a few demographical inequalities in mortality rates were persistent and the reductions in COVID-19-associated mortality rates were not seen among groups that were more likely to demonstrate impaired COVID-19 vaccine efficacy.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.