Results from a small study of eight patients published in Clinical Infectious Diseases suggest that the rebound of COVID-19 is probably not caused by impaired immune responses. The study, led by scientists from the National Institute of Allergies and Infectious Diseases (NIAID), part of the National Institutes of Health, aimed to define the clinical course and the immunological and virological characteristics of the rebound of the COVID -19 in patients who have taken nirmatrelvir. /ritonavir (Paxlovid), an antiviral therapeutic developed by Pfizer, Inc. A COVID-19 rebound is characterized by a recurrence of COVID-19 symptoms and/or a new positive viral test after testing negative, according to the Centers for Disease Control and Prevention. According to the study authors, the results do not support the hypothesis that the five-day course of Paxlovid is too short for the body to develop a strong immune response to SARS-CoV-2, the virus that causes COVID-19.
Participants were selected from adults enrolled in an ongoing COVID-19 study at the NIH Clinical Center in Bethesda, Maryland, and other local hospitals. The study aims to better understand how SARS-CoV-2 affects white blood cells. Participants provide blood and other samples as well as access to their COVID-19 medical records as part of the study. The study to assess the rebound of COVID-19 included six participants (three men and three women with an average age of 42) who took Paxlovid within four days of the initial onset of symptoms and then experienced symptoms recurrent; two participants (a 54-year-old man and a 35-year-old woman) who experienced recurrent symptoms who did not take Paxlovid; and a control group of six people who had COVID-19 but did not experience a rebound in symptoms. All participants were previously vaccinated and boosted against COVID-19, and none developed severe illness requiring hospitalization during acute infection or rebound. The researchers collected data on each participant’s clinical course and performed laboratory tests on blood and nasal swab samples.
The researchers found no evidence of genetic mutations to suggest that the participants who experienced a rebound of COVID-19 were infected with a Paxlovid-resistant strain of SARS-CoV-2. They also found no evidence of delayed antibody development in participants who experienced a rebound after taking Paxlovid. Researchers detected robust SARS-CoV-2 T-cell responses in rebound patients. Overall, the level of T-cell responses was greater in rebound patients than in early acute COVID-19 patients who did not experience rebound. Infectious SARS-CoV-2 was detected by viral culture in one out of eight rebound participants.
According to the authors, the results suggest that rebound symptoms could be partially driven by the robust cellular immune response to residual viral RNA throughout the respiratory tract, rather than an impaired immune response that allows viral replication. Larger and more detailed epidemiologic studies are needed to better understand the clinical significance and epidemiologic consequences of COVID-19 rebound, the authors write. The authors note that the current data support the need for isolation in symptomatic rebound individuals and the need to evaluate, in a clinical trial, longer courses of Paxlovid in immunocompromised individuals where the immune response may be ineffective.
Article
BP Epling, JM Rocco et al. Clinical rebound of COVID-19 after nirmatrelvir/ritonavir is not associated with delayed immune response or severe disease. Clinical Infectious Diseases DOI: 10.1093/cid/ciac663 (2022).
WHO
Irini Sereti, MD, chief of the HIV Pathogenesis Section at the Laboratory of Immunoregulation, part of NIAID’s Division of Intramural Research, is available for comment.
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