Cold, Flu Virus Can Trigger Long COVID Relapses

People who have recovered from long COVID can suffer relapses or flare-ups from new viral infections — not just from COVID but from cold, flu, and other viral pathogens, researchers have found.

In some cases, they may be experiencing what researchers call viral interference, something also experienced by people with HIV and other infections associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Clinical studies on the issue are limited, but patients, doctors, and researchers report many people who previously had long COVID have developed recurring symptoms after consequent viral infections.

Viral persistence — where bits of virus linger in the body — and viral reactivation remain two of the leading suspects for Yale researchers. Viral activation occurs when the immune system responds to an infection by triggering a dormant virus.

Anecdotally, these flare-ups occur more commonly in patients with long COVID with autonomic dysfunction — severe dizziness when standing up — and other symptoms of ME/CFS, said Alba Azola, MD, a Johns Hopkins Medicine rehabilitation specialist who works with patients with long COVID and other “fatiguing illnesses.”

At last count, about 18% of those surveyed by the Centers for Disease Control and Prevention said they had experienced long COVID. Nearly 60% of those surveyed said they had contracted COVID-19 at least once.

Azola said that very afternoon she had seen a patient with the flu and a recurrence of previous long COVID symptoms. Not much data exist about cases like this, she said.

“I can’t say there is a specific study looking at this, but anecdotally, we see it all the time,” Azola said.

She has not seen completely different symptoms; more commonly, she sees a flare-up of previously existing symptoms.

David Putrino, PhD, is director of Rehabilitation Innovation for the Mount Sinai Health System in New York City. He treats and studies patients with long COVID and echoes what others have seen.

Patients can “recover (or feel recovered) from long COVID until the next immune challenge — another COVID infection, flu infection, pregnancy, food poisoning (all examples we have seen in the clinic) — and experience a significant flare-up of your initial COVID infection,” he said.

“Relapse” is a better term than reinfection, said Jeffrey Parsonnet, MD, an infectious diseases specialist and director of the Dartmouth Hitchcock Post-Acute COVID Syndrome Clinic, Lebanon, New Hampshire.

“We see patients who had COVID-19 followed by long COVID who then get better — either completely or mostly better. Then they’ve gotten COVID again, and this is followed by recurrence of long COVID symptoms,” he said.

“Every patient looks different in terms of what gets better and how quickly. And again, some patients are not better (or even minimally so) after a couple of years,” he said.

Patients Tell Their Stories

On the COVID-19 Long Haulers Facebook group, some of the many of the 100,000 ask about viral reactivation. Delainne “Laney” Bond, RN, who has battled postinfection chronic illness herself, runs the Facebook group. From what she sees, “Each time a person is infected or reinfected with SARS-CoV-2, they have a risk of developing long COVID or experiencing worse long COVID. Multiple infections can lead to progressive health complications.”

The posts on her site include many queries about reinfections. A post from December included nearly 80 comments with people describing the full range of symptoms. Some stories relayed how the reinfection symptoms were short-lived. Some report returning to their baseline — not completely symptom-free but improved.

Doctors and patients say long COVID comes and goes — relapsing-remitting — and shares many features with other complex multisystem chronic conditions, according to a new National Academy of Sciences report. Those include ME/CFS and the Epstein-Barr virus.

As far as how to treat, Putrino is one of the clinical researchers testing antivirals. One is Paxlovid; the others are drugs developed for the AIDS virus.

“A plausible mechanism for long COVID is persistence of the SARS-CoV-2 virus in tissue and/or the reactivation of latent pathogens,” according to an explanation of the research on the PolyBio Institute website, which is involved with the research.

In the meantime, “Long COVID appears to be a chronic condition with few patients achieving full remission,” according to a new Academy of Sciences report. The report concludes that long COVID recovery can plateau at 6-12 months. They also note that 18-22% of people who have long COVID symptoms at 5 months are still ill at 1 year.