Study shows long COVID worse for patients than 'long flu'

flu system

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In the 18 months after a serious COVID-19 or seasonal influenza infection, patients are at a significant increased risk of death, hospital readmission, or health problems affecting a number of organs, though COVID patients are hit harder, according to a study published yesterday in The Lancet Infectious Diseases.

The study was led by Ziyad Al-Aly, MD, the chief of research and development at the VA St. Louis Health Care System and a clinical epidemiologist at Washington University. Al-Aly has been studying long COVID for the past 3 years, and has been interested in studying the differences between the acute and chronic phases of the disease.

"With COVID, we first thought if the disease as an acute respiratory illness, but long COVID has raised the public's understating that viral infections can lead to chronic conditions," he told CIDRAP News. "We know Epstein-Barr virus can cause multiple sclerosis; we see post-Ebola conditions develop in survivors; polio infections lead to conditions that appear decades later."

Is COVID truly just like flu?

Al-Aly said the natural comparisons made between COVID-19 and seasonal flu made him eager to understand if influenza infections—those significant enough to require hospitalization—also result in a long-term burden of disease, a "long flu."

Especially after Omicron, you heard people saying COVID is like the flu, or COVID is more of a threat, less of a threat, etcetera.

"Especially after Omicron, you heard people saying COVID is like the flu, or COVID is more of a threat, less of a threat, etcetera," Al-Aly said. When doing a review of the scientific literature, Al-Aly said he found studies comparing COVID and flu outcomes in the short term, only up to 6 months.

In the new study, Al-Aly and his team looked at data from the US Department of Veterans Affairs to assess risk of death, 94 individual health outcomes, the overall burden across all organ systems, hospital readmission, and admission to intensive care units among two groups: 81,280 patients hospitalized for COVID-19 from March 1, 2020, to June 30, 2022, and 10,985 patients hospitalized for seasonal flu from Oct 1, 2015, to Feb 28, 2019.

They assessed outcomes for 18 months.

COVID patients had 50% higher risk of death

Across all time periods, COVID-19 patients had a greater risk of death than seasonal flu patients, at 0 to 30 days (hazard ratio [HR], 2.51; 95% confidence interval [CI], 2.28 to 2.78), 0 to 180 days (HR 1.86), 0 to 360 days (HR 1.61), and 0 to 540 days (HR 1.51). At 18 months, the cumulative death rate for COVID patients was 28.46 per 100 persons, compared with 19.84 per 100 persons for seasonal influenza.

Among the 94 health outcomes assessed in the study, patients who had seasonal flu were more likely to suffer from six outcomes: angina, tachycardia, type 1 diabetes, and three of four pre-specified pulmonary outcomes.

Al-Aly said influenza patients, more than COVID patients, suffered from poor respiratory outcomes. "It seems flu is a more of a respiratory disease, while COVID is a multi-systemic illness; more organs are at risk," Al-Aly said.

But over and over, the study showed outcomes were worse for COVID patients, which Al-Aly said pushes back against the narrative that, in the post-Omicron era, COVID is no more threatening than the flu.

COVID 'much more of a health threat'

"A lot of people trivialize COVID, but even with the mellowing of Omicron, and vaccination, COVID is still much more of a health threat compared to flu," Al-Aly said. "The burden of health loss and burden of disease in post-acute or long phase of the disease is significant."

The COVID-19 group had a higher risk of hospital readmission than the seasonal flu cohort (HR, 1.11; 95% CI, 1.08 to 1.13). And, except for the pulmonary system, COVID patients saw adverse health outcomes across all organ systems at a rate of 615.18 per 100 persons, compared with 536.90 per 100 persons in the seasonal influenza group.

It's critical to note that the health risks were higher after the first 30 days of infection.

"It's critical to note that the health risks were higher after the first 30 days of infection," Al-Aly said in a Washington University news release. "Many people think they're over COVID-19 or the flu after being discharged from the hospital. That may be true for some people. But our research shows that both viruses can cause long-haul illness."

In a commentary on the study, Monica Gandhi, MD, of the University of California–San Francisco, writes that the findings add to the understanding of post-acute health complications.

"The most important finding of this study is the high rate of health outcomes in patients admitted to hospital with COVID-19 and those admitted to hospital with seasonal influenza," Gandhi writes.

"The work by Al-Aly and colleagues, along with that of others, argues for comprehensive studies into the pathophysiology of post-viral syndromes," she adds. "Along with investigation of non-pharmaceutical and pharmaceutical treatments for post-viral syndromes."



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