A recent study concluded that individuals discharged from the hospital after COVID-19 had increased rates of multi-organ dysfunction compared with the expected risk in the general population. Researchers found that diagnosis, treatment and prevention of post-COVID syndrome required integrated rather than organ or disease-specific approaches.

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In a large, well-designed, observational study published in The British Medical Journal on 31 March 2021, a team of researchers from The Office for National Statistics, University College London and University of Leicester, UK reported that people discharged from hospital after COVID-19 appear to have increased rates of organ damage (multi-organ dysfunction) compared with similar individuals in the general population. The organs affected include the heart, kidney and liver.

“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”, a press release from The BMJ said. 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"). However, the long term pattern of organ damage after infection is still unclear.

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Post COVID syndrome/long COVID syndrome

Long COVID, or post-COVID syndrome, is not a condition, and is defined by the National Institute for Health and Care Excellence (NICE) as:

“Signs and symptoms that develop during or after an infection consistent with COVID-19 which continue for more than 12 weeks and are not explained by an alternative diagnosis."

Before, researchers completed the present study, they knew that extra-pulmonary dysfunction, affecting the cardiovascular, metabolic, renal, and hepatic systems, might be associated with COVID-19. They also noted the recent evidence that mortality and readmission after discharge are common in individuals admitted to hospital with COVID-19, but the long term epidemiology of multi-organ morbidity has not been quantified. In fact, these observations inspired them to carry out the research. The team decided to compare and quantify the rates of organ dysfunction in individuals with COVID-19 several months after discharge from the hospital with a matched control group from the general population.

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The study

The study population consisted of 47,780 individuals (mean age 65, 55% men), from the UK National Health Service (NHS) hospitals 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.

The researchers matched the participants with controls, based on personal characteristics and medical history. Using the health records of the participants they tracked rates of hospital readmission (or any admission for controls), death from any cause, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30th September 2020.

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Results

The major findings of the study (verbatim) from the BMJ press release were as follows:

• 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 the 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, 3, 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 diseases.
• Differences in disease rates between men and women were generally small.

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Conclusions

The researchers concluded that individuals discharged from the hospital after COVID-19 had increased rates of multi-organ 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 required integrated rather than organ or disease-specific approaches.

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 the hospital with COVID-19. The researchers pleaded for carrying out urgent research to understand the risk factors for post-COVID syndrome so that the treatment can be targeted better to demographically and clinically at-risk populations.

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Implications of the study

When researchers wrote the study, over three million people in the UK had tested positive for COVID-19 and many more who had the disease had never received a test. Their study suggested that the long term burden of COVID-19 related morbidity on hospitals and broader healthcare systems might be substantial.

While organ dysfunction in in-hospital patients represents only part of the problem, other symptomatic manifestations of the post-COVID syndrome in individuals not requiring admission to hospitals have the potential to be debilitating, placing a considerable burden on healthcare resources, particularly in primary care.

Post-COVID syndrome adds to current healthcare challenges, particularly sustainable high quality care for long term conditions like:

• Inequalities in health
• Access and provision
• Incomplete pathways across community and hospital care
• Need to translate research into clinical practice with sufficient resources

"Our findings across organ systems suggests that the diagnosis, treatment, and prevention of post-COVID syndrome requires integrated rather than organ or disease-specific approaches. Integrated care pathways, effective in other diseases, such as chronic obstructive pulmonary disease, could be useful in the management of the post-COVID syndrome," they clarified.

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Strengths and limitations of the study

• The study included all individuals in England admitted to hospital with COVID-19 observed over a follow-up period of several months, matched to general population controls from 10 years of clinical records. It was also a complete study.
• In an observational study, some confounding results are possible, because biomarkers or socioeconomic factors were omitted from the matching set. The number of events in the control group were limited. Because of this deficiency, researchers could not disaggregate rate ratios stratified by age and ethnicity beyond ages less than 70 versus 70 or older and white versus non-white groups, despite likely variations in outcomes within these groups.
• The individuals with undiagnosed hypertension and diabetes were classified as not having these conditions as the researchers did not consider blood pressure and measurements of glycated haemoglobin when defining matching variables. As a result of the Quality and Outcomes Framework (pay for performance), however, primary care coding for hypertension and diabetes is generally of high quality.
• The researchers admitted that performing multiple imputations for missing values was not practical because of the size of the study dataset, instead, they adopted the missing indicator approach, which could cause some bias in non-randomised studies. But the missing mechanism in clinical records might to some extent be “missing not at random” (e.g. individuals who are neither underweight nor overweight could be less likely to have their body mass index measured), which would preclude the use of standard imputation techniques.
• In a Rapid Response to the article, Dr Gareth H Jones, Tribunal doctor, Mental Heart Tribunal for Wales noted that the vulnerabilities to COVID include many problems of Western diet and lifestyle, including metabolic syndrome, non-alcoholic fatty liver disease, and poor cardiovascular fitness due to too little exercise. This paper demonstrates that these problems are worsened, or initiated, by having COVID.

“Much of this could be explained by accelerated ageing due to COVID infection, and I would suggest we look at measures of ageing in sufferers, including tests such as telomere length. Such tests might contribute to our understanding of long COVID," he suggested.

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The impact of the study in India

Recently, the Union Health Ministry disclosed that eight states which include Maharashtra, Karnataka and Punjab have reported a high number of daily COVID-19 cases and account for 84.5% of the 68,020 fresh cases recorded in the country in a day. The numbers are steadily increasing. If as shown in the present study, a notable fraction of the patients suffer from cardiovascular diseases, and damage to vital organs such as the heart, kidney and liver on a daily basis. Our healthcare system which is already under tremendous strain will not be able to face the challenge.

We cannot afford to have more patients. While the State and Central governments enforce viable restrictions to combat the virus, the public must strictly comply with COVID norms like universal masking, hand washing, physical distancing, and avoiding crowds even when vaccinations are available. This can go a long way in vanquishing the virus. People must get vaccinated promptly when their turn comes. They must intervene politely if anyone violates the norms. Disobeying COVID-19 norms is an antisocial activity.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

Dr K S Parthasarathy is a former Secretary of the Atomic Energy Regulatory Board and a former Raja Ramanna Fellow, Department of Atomic Energy. A Ph. D. from the University of Leeds, UK, he is a medical physicist with a specialisation in radiation safety and regulatory matters. He was a Research Associate at the University of Virginia Medical Centre, Charlottesville, USA. He served the International Atomic Energy Agency as an expert and member in its Technical and Advisory Committees.