Complications Common Even in Younger COVID-19 Patients

Liam Davenport

July 16, 2021

Almost half of patients, regardless of age, admitted to hospital with COVID-19 develop at least one complication, which can have a significant impact on their ability to look after themselves after they are discharged, suggests a large UK prospective study.

With complications and poor outcomes common even among younger patients, the researchers say the results underline the importance of vaccination and appropriate healthcare planning.

The research was published by The Lancet on July 17.

Contradicting Current Narratives

The team studied more than 73,000 UK patients admitted to hospital with COVID-19 between January and August 2020, of whom almost 50% developed at least one complication, ranging from 39% in those aged 19–49 years to 51% in older patients.

The most common complications were renal, complex respiratory and systemic, and they had an ongoing impact on patient health, leaving 27% less able to take care of themselves after discharge, including 13% of those aged 19–29 years.

"This work contradicts current narratives that COVID-19 is only dangerous in people with existing comorbidities and the elderly," commented joint chief investigator Calum Semple, professor of child health and outbreak medicine, University of Liverpool, in a news release.

"Dispelling and contributing to the scientific debate around such narratives has become increasingly important," he continued. "Disease severity at admission is a predictor of complications even in younger adults, so prevention of complications requires a primary prevention strategy, meaning vaccination."

Joint senior author Professor Ewen Harrison, from the Centre for Medical Informatics, Usher Institute, University of Edinburgh, agreed that their work underlines the importance of COVID-19 vaccination.

"The results can also inform public health messaging on the risk COVID-19 poses to younger otherwise healthy people at a population level, particularly in terms of the importance of vaccination for this group."

Moreover, the results highlight "some insightful patterns and trends that can inform healthcare systems and policy maker responses to the impacts of COVID-19".

Co-author Dr Thomas Drake, Centre for Medical Informatics, Usher Institute, University of Edinburgh, emphasised that the study also shows the importance of considering "not just death from COVID-19, but other complications as well".

He added: "We are still studying the participants in our study to understand the long-term effects of COVID-19 on their health.

"The results from these ongoing studies will be particularly useful, as we found many people who survive COVID-19 and develop complications are from economically active age groups."

Aya Riad, a medical student at the University of Edinburgh, and co-author of the study, said understanding this is crucial when "making decisions on how best to tackle the pandemic".

"Just focussing on death from COVID-19 is likely to underestimate the true impact, particularly in younger people who are more likely to survive severe COVID-19."

Organ Support

Previous studies of patients hospitalised with COVID-19 have indicated that they have mortality rates of approximately 26%, and up to 17% require ventilatory support and critical care.

The researchers note that a "substantial proportion of patients with COVID-19 go on to develop critical illness and require organ support", leading to "substantial" additional physical and mental health morbidity.

However, the wide use of mortality as an outcome in epidemiological studies has failed to capture "the immediate short-term health issues faced by survivors, including in-hospital complications and functional outcomes".

To investigate further, the team conducted a prospective, multi-centre cohort study of patients aged 19 years or over with confirmed or highly suspected COVID-19 at 302 healthcare facilities in the UK.

Nurses and medical students collected baseline demographic and health-related data, including the presence of comorbidities such as chronic cardiac, haematological, kidney, neurological or pulmonary disease, asthma, HIV/AIDS, cancer, liver disease, obesity, and rheumatological disorders.

They also collected data on the respiratory, neurological, cardiovascular, renal, gastrointestinal and systemic complications participants experienced while in hospital, and the ability of patients to look after themselves when they were discharged.

Between 17 January and 4 August, 2020, 75,276 eligible patients aged 19 years or over were included. Among those, 73,197 (97.2%) had complication data available for analysis.

The mean age of the patients was 71.1 years, 56.0% were male and 81.0% had at least one comorbidity. Chronic cardiac disease was the most common (30.8%), followed by diabetes (24.2%), chronic pulmonary disease (16.7%) and chronic kidney disease (16.6%).

The overall mortality rate in the cohort was 31.5%, and 49.7% of patients had at least one complication. Among patients who survived, 43.5% had at least one complication.

Having any complication was found to be significantly associated with critical care admission, at an odds ratio of 7.25 (p<0.0001), and with mortality, at a hazard ratio of 1.74 (p<0.0001).

Risk Factors

Men were more likely to have at least one complication than women, as were patients aged 60 years and over.

Among patients aged over 60 years, the complication rate was 54.5% in men versus 48.2% in women, while in those aged less than 60 years the complication rate was 48.8% in men and 36.6% in women.

The incidence rose with increasing age, from 27% among 19 to 29-year-olds hospitalised with COVID-19 to 37% in 30 to 39-year-olds, 43% among 40 to 49-year-olds and 51% of people aged 50 years and over.

Black patients were also more likely to experience complications than White people, at 58% versus 49%.

The most common complications were renal, which were seen in 24.3% of patients, followed by complex respiratory (18.4%) and systemic (16.3%) complications.

Cardiovascular complications were recorded in 12.3% of patients, while gastrointestinal and liver complications were seen in 10.8%, and neurological complications in 4.3%.

The most common individual complications were acute kidney injury, probable acute respiratory distress syndrome, liver injury, anaemia, and cardiac arrhythmia.

Following hospitalisation, 27% of patients were less able to take care of themselves than they had been before they had COVID-19, an outcome that was associated with older age, being male, and receipt of critical care.

The team calculates that having any complication was associated with a significantly worse ability to self-care following discharge, at an odds ratio of 2.42 (p<0.0001).

'Inspiring Ideas'

In an accompanying comment, Dr Xiaoying Gu and Professor Bin Cao, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, say the study provides "inspiring ideas" for further study.

"One of the most notable findings…is that the relative risk of death is much higher in younger patients with complications when compared with those of the same age who did not suffer a complication, whereas in older patients, the relative impact of complications on mortality appears to be lower," they say

This "indicates that attention should also be paid to younger patients who are less likely to die during the acute phase but more likely to live longer with complications in the days after acute or subacute COVID-19", they write.

The long-term consequences of in-hospital COVID-19 complications need to be examined, they say, as well as the impact of ethnicity and socioeconomic factors.

This work is supported by grants from the National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Imperial Biomedical Research Centre, HPRU in Respiratory Infections at Imperial College London, and NIHR HPRU in Emerging and Zoonotic Infections at the University of Liverpool, in partnership with Public Health England, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, Liverpool Experimental Cancer Medicine Centre, NIHR Biomedical Research Centre at Imperial College London, EU Platform for European Preparedness Against (Re-) Emerging Epidemics.

Prof Semple reports grants from DHSC, NIHR UK, MRC UK, HPRU in Emerging and Zoonotic Infections, and University of Liverpool, during the conduct of the study; and is chair of the Infectious Diseases Science Advisory Board and minority shareholder of Integrum Scientific, Greensboro NC, outside the submitted work.

No other relevant financial relationships declared.

Lancet 2021; 398: 223–37 doi: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00799-6/fulltext

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