Another Face of Long COVID: Kidney Disease

In April 2021, we published the largest comprehensive analysis providing systematic characterization of all the

In April 2021, we published the largest comprehensive analysis providing systematic characterization of all the post-acute sequelae of COVID-19. The study showed that beyond the acute phase of the disease, COVID-19 can result in several extrapulmonary manifestations including acute and chronic kidney disease. Following the publication of that study, we received numerous requests from patients, scientists, physicians, and other stakeholders in the nephrology community urging us to perform a dedicated analysis diving deeper into the long-term consequences of COVID-19 infection on kidney health and disease. This led us to conduct the largest study to-date involving 89,216 people with COVID-19 and 1,637,467 non-infected controls to evaluate the risks of several kidney outcomes (including acute and chronic kidney disease) in the post-acute phase of COVID-19.

What We Know

In this study, which was recently published in the Journal of the American Society of Nephrology, my colleagues and I found that in the post-acute phase of the disease, people with COVID-19 are at increased risk of acute kidney injury, chronic kidney disease, and end-stage kidney disease. We reported that this increased risk is evident even in people whose disease was mild and did not necessitate hospitalization during the acute phase of the infection — those patients represent the majority of people with COVID-19. We also found that the risk was greater in people who needed to be hospitalized and greatest in those who needed intensive care during the acute phase of the disease.

Our studies estimate that around 13.44 per 1,000 people with COVID-19 go on to develop some form of kidney injury or disease. Given that nearly 44 million people have been infected with COVID-19 in the U.S., we estimate that more than half a million people will have some form of kidney disease as a result of long-COVID. This will add to the already substantial burden of kidney disease in the U.S.

Our studies also show remarkable loss of estimated glomerular filtration rate (eGFR) among people who survive the acute phase of COVID-19. Among those who were not hospitalized for COVID-19 during the acute phase of the disease, they exhibited eGFR loss attributable to COVID-19 at an annualized rate of -3.26 ml/min/1.73 m2 — the equivalent of aging an extra 3 years. Among those who were hospitalized, the eGFR loss attributable to COVID-19 was more than 7.69 ml/min/1.73 m2 — the equivalent of aging more than 7 additional years.

Implications

While we still do not fully understand why SARS-CoV-2 — a respiratory virus — induces broad extrapulmonary organ dysfunction including acute and chronic kidney damage and loss of kidney function, the broader implications of the evidence are clear. COVID-19 will substantially contribute to a rise in the incidence of acute kidney injury and chronic kidney disease. Healthcare providers, health systems, and governments must be aware of this reality, and must develop strategies for early identification and treatment of these patients. The overarching goal would be to reduce the risk of progression to more severe forms of kidney disease and to mitigate the cardiometabolic consequences and early death that generally characterize advanced chronic kidney disease.

The cost of developing early detection and prevention strategies will certainly help contain much larger downstream costs in terms of loss of life and cost of caring for end stage kidney disease.

Long-COVID is a multifaceted disease. It is now abundantly clear that some clinical manifestations of long-COVID, such as fatigue, may resolve with time in some people; but it is also abundantly clear that long-COVID results in chronic conditions such as chronic kidney disease (and other non-communicable disease such as heart failure, and new onset diabetes). These are manageable — but not curable — diseases that will affect people for a lifetime. And all these conditions are associated with greater need for utilization of healthcare resources, decreased quality of life, increased risk of death, and reduced life expectancy. The added burden of kidney disease and other non-communicable diseases will have far-reaching implications, not only on health outcomes and life expectancy, but also more broadly on social, economic, and political issues.

COVID-19 will cast a tall shadow in the form of long-COVID that will shape our lives for decades to come. We got caught unprepared for COVID-19 and delivered a dismal public health response that caused a significant toll of suffering, disease, and death — much of it could have been avoided. Let’s learn from our failure and be prepared to deal with long-COVID.

Ziyad Al-Aly, MD, is a physician scientist, clinical epidemiologist, and long COVID researcher. He is the director of the Clinical Epidemiology Center and the chief of Research and Development Service at Veterans Affairs St. Louis Health Care System in Missouri.