People discharged from hospital after COVID-19 appear to have increased rates of organ damage ("multiorgan dysfunction") compared with similar individuals in the general population, finds a study. The increase in risk was not confined to the elderly and was not uniform across ethnic groups, prompting the researchers to suggest that the long-term burden of COVID-19-related illness on hospitals and broader healthcare systems is likely to be substantial.
Although COVID-19 is most well known for causing serious respiratory problems, it can affect other organs and systems within the body, including the heart, kidneys, and liver.
Several unexplained symptoms that continue for more than 12 weeks after COVID-19 are said to be part of post-COVID syndrome (also known as "long COVID"), but the long term pattern of organ damage after infection is still unclear.
To investigate this, a team of UK researchers from the Office for National Statistics, University College London and University of Leicester set out to compare rates of organ dysfunction in individuals with COVID-19 several months after discharge from hospital with a matched control group from the general population.
Their findings are based on 47,780 individuals (average age 65, 55% men) in hospital in England with COVID-19 who were discharged alive by 31 August 2020.
Participants were matched with controls, based on personal characteristics and medical history. Health records were then used to track rates of hospital readmission (or any admission for controls), death from any cause, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30 September 2020.
Over an average follow-up of 140 days, nearly a third of individuals who were discharged from hospital after acute COVID-19 were readmitted (14,060 of 47,780) and more than 1 in 10 (5,875) died after discharge.
These events occurred at rates of 766 readmissions and 320 deaths per 1,000 person years, which were four and eight times greater, respectively, than those in matched controls.
Rates of respiratory disease, cardiovascular disease, and diabetes were also significantly raised in patients with COVID-19, with 539, 66, and 29 new onset diagnoses per 1,000 person years, respectively (equivalent to 27, three, and 1.5 times greater than in matched controls).
Differences in rates of multiorgan dysfunction between patients with COVID-19 and matched controls were greater for individuals aged less than 70 than for those aged 70 or older, and in ethnic minority groups compared with the white population, with the largest differences seen for respiratory disease.
Differences in disease rates between men and women were generally small.
This was a large, well-designed study using 10 years of historical clinical records to exactly match individuals with COVID-19 to controls. However, the findings are observational, and the authors cannot rule out the possibility that rates of diagnoses in general might have decreased indirectly because of the pandemic, particularly in people not admitted to hospital with COVID-19.
"Our findings suggest that the diagnosis, treatment, and prevention of post-COVID syndrome requires integrated rather than organ or disease specific approaches," they write.
And they say urgent research is needed "to understand the risk factors for post-COVID syndrome so that treatment can be targeted better to demographically and clinically at risk populations."
"The importance of long term chronic conditions such as diabetes and cardiovascular disease is underlined, not only as risk factors for hospitalisation and mortality from covid-19, but also as medium- to long-term complications of infection in hospitalised individuals after recovery," writes senior author Dr Amitava Banerjee, in a corresponding BMJ blog post.
"In addition to the respiratory, cardiac, renal, and endocrine pathology shown by this population level study and others, clusters of patients seem to have features of immunological dysfunction, dysautonomia, mast cell dysfunction, and neurological diagnoses," write Dr Manoj Sivan; Clare Rayner; and Brendan Delaney a BMJ editorial.
Post-COVID syndrome in individuals admitted to hospital with covid-19: retrospective cohort study
Daniel Ayoubkhani, Kamlesh Khunti, Vahé Nafilyan, Thomas Maddox, Ben Humberstone, Ian Diamond, Amitava Banerjee
Published in BMJ on 31 March 2021
To quantify rates of organ specific dysfunction in individuals with covid-19 after discharge from hospital compared with a matched control group from the general population.
Retrospective cohort study.
NHS hospitals in England.
47 780 individuals (mean age 65, 55% men) in hospital with covid-19 and discharged alive by 31 August 2020, exactly matched to controls from a pool of about 50 million people in England for personal and clinical characteristics from 10 years of electronic health records.
Main outcome measures
Rates of hospital readmission (or any admission for controls), all cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30 September 2020. Variations in rate ratios by age, sex, and ethnicity.
Over a mean follow-up of 140 days, nearly a third of individuals who were discharged from hospital after acute covid-19 were readmitted (14 060 of 47 780) and more than 1 in 10 (5875) died after discharge, with these events occurring at rates four and eight times greater, respectively, than in the matched control group. Rates of respiratory disease (P<0.001), diabetes (P<0.001), and cardiovascular disease (P<0.001) were also significantly raised in patients with covid-19, with 770 (95% confidence interval 758 to 783), 127 (122 to 132), and 126 (121 to 131) diagnoses per 1000 person years, respectively. Rate ratios were greater for individuals aged less than 70 than for those aged 70 or older, and in ethnic minority groups compared with the white population, with the largest differences seen for respiratory disease (10.5 (95% confidence interval 9.7 to 11.4) for age less than 70 years v 4.6 (4.3 to 4.8) for age ≥70, and 11.4 (9.8 to 13.3) for non-white v 5.2 (5.0 to 5.5) for white individuals).
Individuals discharged from hospital after covid-19 had increased rates of multiorgan dysfunction compared with the expected risk in the general population. The increase in risk was not confined to the elderly and was not uniform across ethnicities. The diagnosis, treatment, and prevention of post-covid syndrome requires integrated rather than organ or disease specific approaches, and urgent research is needed to establish the risk factors.
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