COVID-19 rebound not due to impaired immune response, small study suggests
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COVID-19 rebound in people who have recovered from the disease is not due to an impaired immune response, according to a small study of patients treated with and without Paxlovid.
The study sought to examine whether a weakened immune system, possibly because of treatment, caused a resurgence of symptoms in patients treated with the drug. Researchers found that patients who tested negative for SARS-CoV-2 and who were thought to have recovered experienced the rebounds for reasons not related to the immune system.
“We did this study out of concern that very early antiviral treatment was quickly suppressing the virus with a subsequent lack of development of natural immune response — ‘immune evasion’ — which could be troublesome because re-emerging or residual virus could cause disease progression,” Irini Sereti, MD, MHS, an infectious disease physician scientist and senior investigator at the NIH, told Healio.
“Also, the extra benefit of natural infection-induced response on top of previous vaccination would be lost,” said Sereti.
Sereti and colleagues evaluated 14 patients: six with rebound COVID-19 after Paxlovid treatment; two with rebound COVID-19 who did not receive Paxlovid; and six with COVID-19 cause by the omicron variant who did not experience a rebound.
The six rebound patients treated with Paxlovid received the drug between 1 and 4 days after initial symptom onset, and all rebound patients “experienced significant symptomatic improvement prior to worsening,” the researchers wrote. The patients tested negative for SARS-CoV-2 as their symptoms improved, and as symptoms worsened again, positive PCR tests were returned for the patients.
Among these six rebound patients, who Sereti said motivated the study, none developed severe disease symptoms during the rebound period or required additional treatment.
Additionally, the researchers reported that high levels of neutralizing antibodies were found in all patients and that these antibodies were seen at increased levels in all rebound patients — suggesting that rebound symptoms were not due to an impaired immune response.
“It is important to understand what is really happening in detail in the tissue, as this seems to be part of the natural history of the viral infection, but it is unclear why the antiviral use does not prevent it. In my opinion, we need studies of longer durations of Paxlovid to see if a more prolonged initial course can further suppress the virus and prevent these rebounds,” Sereti said.
Patients early in the pandemic — before Paxlovid was available — also reported having COVID-19 in “two phases,” and this “seems to be more a part of the viral infection,” Sereti said. “The question is, ‘Why doesn’t Paxlovid change that?’”
She noted, however, that not only has the virus changed, but so has the host because of vaccines and a variety of medications. This, she said, is how SARS-CoV-2 now survives better in the upper respiratory tract rather than the lower — it has evolved along with the people it infects.
“It becomes a very complex interplay between the virus and the treatments coming out and the host because everybody is different,” Sereti said. “The thing is now we know about it, and we warn people that this may happen.”
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