How does long COVID affect the kidneys? Study investigates

  • Researchers have uncovered a trajectory of significant kidney impairment in people with long COVID 30 days after infection.
  • Adverse kidney outcomes increased in line with the severity of people’s acute SARS-CoV-2 infections.
  • The public health costs and quality-of-life implications for people with long COVID and chronic kidney disease are significant.

Scientists working at the Veterans Administration (VA) St. Louis Health Care System and the Washington University School of Medicine, also in St. Louis, have revealed jarring results regarding kidney impairment in some people with long COVID, or post-acute sequelae of COVID-19 syndrome (PASC).

These physician-researchers and epidemiologists uncovered alarming data regarding the effects of SARS-CoV-2 on people with varying degrees of illness severity.

The study findings appear in the Journal of the American Society of Nephrology.

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Leveraging the broad reach of the VA Health Care System to follow and clinically study people, this investigation augmented previous outcomes from the largest study to date of people experiencing PASC symptoms. That research is by the same authors.

In an interview for Medical News Today, Dr. Al-Aly noted that he and his colleagues embarked on this research inspired by their patients’ complaints of persistent, debilitating symptoms post-acute COVID-19.

“That launched us into COVID-19 research to start with, that feedback from the patient community. [W]e knew at this point that we need to look at this — we need to look at the broad picture of long COVID.”

He further observed: “The main message was [that] long COVID could affect every organ system. And we knew it could affect the kidney. [W]e wanted to do a deep dive into the long-term consequences of COVID-19 on kidney function and kidney disease. That is the story that led us here.”

Comparing kidney function in people with and without SARS-CoV-2

The researchers stratified and compared patients in two arms: individuals who had a SARS-CoV-2 infection and those who did not.

They further funneled the study participants into groups of people with COVID-19 who survived for 30 days compared with groups of non-COVID-19 patients who had recent kidney function blood work within the researchers’ “ground-zero” study date (T₀ + 30 days).

Then, the scientists streamlined people with post-acute COVID-19 by the severity of their disease:

  • non-hospitalized people
  • hospitalized people
  • people requiring intensive care units (ICUs)

Based on this study design, the scientists garnered a huge number of participants. There were a total of 1,726,683, of whom 89,216 were post-acute COVID-19 survivors.

In addition, the researchers assessed complicating health and socioeconomic factors known to affect kidney health.

Using statistical analysis, the epidemiologists “subtracted” these pre-study health influences so that people who had survived COVID-19 and those who did not have a SARS-CoV-2 infection were justifiably comparable.

Dr. Al-Aly commented: “We wanted […] to control for all these covariates and make sure we were isolating the pure effect of COVID-19 on these outcomes. We were interested in seeing: Does COVID-19 itself give us, in the long term, [a] higher risk of AKI [acute kidney insufficiency]? Or eGFR [estimated glomerular filtration rate] decline? Or ESKD [end stage kidney disease]?”

The impact of long COVID on kidney function

The scientists’ results revealed the following:

  • People who had contracted SARS-CoV-2 had a greater risk of kidney damage and disease in the period following 30 days after infection than those who did not have SARS-CoV-2.
  • The severity of kidney outcomes matched the severity of the patients’ acute SARS-CoV-2 infections.
  • Hospitalized patients who experienced AKI experienced a greater long-term decrease in kidney function than non-hospitalized people with AKI.

Dr. Al-Aly noted, “We were expecting to see some kidney problems in people who were really sick and needed to be in the ICU from COVID-19.”

“The most surprising thing was that even […] people who had relatively mild disease and did not need hospitalization […] went on to develop kidney problems: AKI, decline in GFR, and ESKD. And that’s the really alarming point: because these non-hospitalized people are the majority of people in the [United States] who had COVID-19. That was, I think, the most important message from a broad public health perspective.”

He added: “It’s alarming to have 1.46 per 1,000 persons develop (decrease in GFR). You think, ‘Oh, that’s really small, only 1.46 persons per 1,000 patients.’ But if you multiply that by 38 million [people in the U.S.] who have documented COVID-19, well then, 1.46 persons per 1,000 translates to huge numbers on a population scale.”

Narrowing the research perspective to the individual, Dr. Al-Aly observed that people with long COVID “can have a 30% decline in GFR and feel nothing. It’s silent, it’s painless […]. Honestly, that is why we want to alert the medical community at large, because this is a silent disease.”

He also noted that a major decline in kidney function occurs in the first 120 days and then levels off. When queried as to the real-life consequences for patients, Dr. Al-Aly recalls that in his long COVID clinic, “The GFR (for a patient) before COVID-19 was 80 and now, all of a sudden, it’s 45 (ml/min/1.73 m²). [I]t’s almost as if the kidney is aging 30 years in 3 or 4 months!”

The physician-researchers do not speculate on the etiology of the kidney damage observed in long COVID. Dr. Al-Aly said: “Long COVID is not one thing, it’s not only kidney dysfunction. People want to know why a respiratory virus — like SARS CoV-2 — can give you brain fog. Why would a respiratory virus […] give us kidney problems, why would it do that? The short answer is: We don’t know.”

Study strengths and limitations

The scientists acknowledge limitations to their study. Firstly, studying veterans — a group consisting mainly of older, white males — skews the study population, possibly reducing the ability to generalize findings to other populations.

Additionally, estimates of illness severity were limited to intensity of care (level of hospitalization), eschewing other severity measures.

Finally, the researchers acknowledge that new developments in the pandemic, including virus variants and the effects of vaccination, will possibly influence epidemiologic follow-up of post-acute COVID-19 kidney outcomes.

Dr. Al-Aly recounted: “When COVID-19 started, we re-tooled our shop to answer questions related to COVID-19. We didn’t do all this last year. We perfected these different methodologies over the past decade. Now, we leveraged every ounce of power, everything we know, to address those questions that we think are important from a public health perspective.”

In summary, people with post-acute COVID-19 show a higher risk of significant kidney impairment from moderate-to-severe health outcomes. The researchers recommend integrating kidney care into post-acute COVID care pathways.

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