Home Cellular science COVID bounces back: Immune responses can be jump-started by cleaning up viral remnants

COVID bounces back: Immune responses can be jump-started by cleaning up viral remnants

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

Pfizer’s Paxlovid antiviral pill is one of the most valuable tools in hammering COVID-19; it can reduce the relative risk of hospitalization and death by 89% in unvaccinated patients at high risk of severe disease. But, as the use of this convenient drug has grown in the United States, so have the troubling reports of rebound cases – people who took the pill early in their infection, started feel better and even tested negative, but then relapsed into symptoms and tested positive again. days later.

It is still unclear how common the phenomenon is, but it certainly occurs in a certain proportion of patients treated with Paxlovid. In May, the Centers for Disease Control and Prevention even published a health alertt on rebound reports.

But, amid growing awareness, it has also become clear that patients who have not been treated with Paxlovid can also rebound. In fact, in Pfizer’s clinical trials of Paxlovid, researchers noted that about 1-2% of the treatment and placebo groups had rebounds.

Taken together, this raised a host of questions: Did the rebounds revive infections? Are people still contagious? Should they resume isolation? Are they at risk of serious illness again? Has their immune system failed to mount an effective response? Does the virus mutate to become resistant to Paxlovid? Does Omicron cause more bounce than previous variants?

Data so far is limited and mostly only anecdotal reports. But a new small pre-print study by researchers at the National Institutes of Health offers encouraging news about COVID rebounds. The study, which included data on seven rebounding patients – six of whom were treated with Paxlovid and one who was not – found no evidence of Paxlovid-resistant mutations, wild-type viral replication or responses weak immune systems.

Intact immune responses

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

Together, the findings suggest the rebounds may be partly due to a reignited immune response as the body works to clear cellular debris and viral remnants from a quickly snuffed out infection. Or, as the authors put it: “rebound symptoms may in fact be partially caused by the emerging immune response against residual viral antigens possibly excreted by dying infected cells due to cytotoxicity and tissue repair in the pathways respiratory”.

In support of 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 virus at the time of their rebound. And this patient also had underlying immunosuppression, which may explain the finding. Moreover, none of the rebounding patients developed serious illness.

The study is, again, very small and may not be generalizable to all cases of rebound. The authors call for rebound studies with larger cohorts. But some elements of the conclusions are already substantiated. For example, other studies have also failed to identify Paxlovid-resistant mutations. And on Tuesday, the CDC published a study of more than 5,000 patients treated with Paxlovidfinding that less than 1% of patients had emergency department visits or hospitalizations during the 5 to 15 post-treatment rebound period.

So far, the NIH researchers find their new findings “encouraging.” As Epling wrote in a tweet tuesday“The results suggest that “an appropriate immune response develops, so rebound is not caused by people not developing an immune response to COVID while on Paxlovid.”