COVID rebounds: Immune responses may be reignited by cleanup of viral scraps

COVID rebounds: Immune responses may be reignited by cleanup of viral scraps

Enlarge / A box of Paxlovid, Pfizer’s antiviral drug.

Pfizer’s Paxlovid antiviral pill is among the most prized tools to combat COVID-19; it can reduce the relative risk of hospitalization and death by 89 percent in unvaccinated patients at high risk of severe disease. But, as use of the convenient drug has grown in the US, so have worrying reports of rebound cases: People who took the pill early in their infection began to feel better and even gave up. negative, but then they had symptoms again and tested positive again. days after.

It is not yet clear how common the phenomenon is, but it certainly occurs in a proportion of patients treated with Paxlovid. In May, the Centers for Disease Control and Prevention even issued a health alert about rebound reports.

But, amid growing awareness, it has also become clear that patients who have not been treated with Paxlovid can also recover. In fact, in clinical trials of Pfizer’s Paxlovid, researchers found that between 1 and 2 percent of the treatment and placebo groups rebounded.

Taken together, this has raised a number of questions: are rebounds rekindled infections? Are people still infectious? Do they need to resume isolation? Are they again at risk of serious illness? Were their immune systems unable to mount an effective response? Is the virus mutating to become resistant to Paxlovid? Is Omicron causing more bounces than previous variants?

So far, there is limited data and mostly just anecdotal reports. But a new small preprint study led by researchers at the National Institutes of Health offers some encouraging news about COVID rebounds. The study, which included data on seven rebound patients, six of whom were treated with Paxlovid and one who was not, found no evidence of Paxlovid-resistant mutations, uncontrolled viral replication, or faltering immune responses.

intact immune responses

Instead, a detailed look at their immune responses found that rebounds were associated with increased SARS-CoV-2-specific antibody and cellular immune responses. At the same time, the rebounds were accompanied by downward trends in markers of innate (non-specific) immune responses, as well as levels of SARS-CoV-2 nucleocapsid fragments in the blood.

Together, the findings suggest that the rebounds could be due in part to a reactivated immune response as the body works to clear cellular debris and viral remnants of a quickly quelled infection. Or, as the authors put it: “rebound symptoms may, in fact, be driven in part by the emergent immune response against residual viral antigens possibly shed by infected cells dying due to cytotoxicity and repair.” of tissues throughout the respiratory tract.

To further support this, the authors, co-led by infectious disease experts Brian Epling and Joe Rocco, note that while three of the four controls had recoverable live virus during their acute infection, only one of the seven rebounding patients had a live virus. live virus. virus at the time of its rebound. And that patient also had underlying immunosuppression, which could explain the finding. Furthermore, none of the patients who rebounded developed severe disease.

The study is again very small and may not be generalizable to all rebound cases. The authors call for rebound studies with larger cohorts. But some elements of the findings are already supported. For example, other studies also failed to identify Paxlovid-resistant mutations. And on Tuesday, the CDC released a study of more than 5,000 Paxlovid-treated patients, finding that fewer than 1 percent of patients had emergency visits or hospitalizations in the 5- to 15-day recovery period after treatment.

For now, NIH researchers call the emerging picture “encouraging.” Epling wrote in a tweet on tuesday that the findings suggest that “an adequate immune response is developing, so the rebound is not caused by people who do not develop an immune response to COVID while taking Paxlovid.”

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