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Clinical, Virologic, and Immunologic Evaluation of Symptomatic Coronavirus Disease 2019 Rebound Following Nirmatrelvir/Ritonavir Treatment.
Epling, Brian P; Rocco, Joseph M; Boswell, Kristin L; Laidlaw, Elizabeth; Galindo, Frances; Kellogg, Anela; Das, Sanchita; Roder, Allison; Ghedin, Elodie; Kreitman, Allie; Dewar, Robin L; Kelly, Sophie E M; Kalish, Heather; Rehman, Tauseef; Highbarger, Jeroen; Rupert, Adam; Kocher, Gregory; Holbrook, Michael R; Lisco, Andrea; Manion, Maura; Koup, Richard A; Sereti, Irini.
  • Epling BP; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Rocco JM; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Boswell KL; Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Laidlaw E; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Galindo F; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Kellogg A; Clinical Research Directorate, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, Maryland, USA.
  • Das S; Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
  • Roder A; Systems Genomics Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Ghedin E; Systems Genomics Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Kreitman A; Systems Genomics Section, Laboratory of Parasitic Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Dewar RL; Virus Isolation and Serology Laboratory, Frederick National Laboratory, Frederick, Maryland, USA.
  • Kelly SEM; Trans-NIH Shared Resource on Biomedical Engineering and Physical Science, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
  • Kalish H; Trans-NIH Shared Resource on Biomedical Engineering and Physical Science, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
  • Rehman T; Virus Isolation and Serology Laboratory, Frederick National Laboratory, Frederick, Maryland, USA.
  • Highbarger J; Virus Isolation and Serology Laboratory, Frederick National Laboratory, Frederick, Maryland, USA.
  • Rupert A; AIDS Monitoring Laboratory, Frederick National Laboratory, Frederick, Maryland, USA.
  • Kocher G; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
  • Holbrook MR; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
  • Lisco A; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Manion M; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Koup RA; Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Sereti I; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Clin Infect Dis ; 2022 Oct 06.
Article in English | MEDLINE | ID: covidwho-2258289
ABSTRACT

BACKGROUND:

Nirmatrelvir/ritonavir, the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease inhibitor, reduces the risk of hospitalization and death by coronavirus disease 2019 (COVID-19) but has been associated with symptomatic rebound after therapy completion.

METHODS:

Six individuals with relapse of COVID-19 symptoms after treatment with nirmatrelvir/ritonavir, 2 individuals with rebound symptoms without prior antiviral therapy and 7 patients with acute Omicron infection (controls) were studied. Soluble biomarkers and serum SARS-CoV-2 nucleocapsid protein were measured. Nasal swabs positive for SARS-CoV-2 underwent viral isolation and targeted viral sequencing. SARS-CoV-2 anti-spike, anti-receptor-binding domain, and anti-nucleocapsid antibodies were measured. Surrogate viral neutralization tests against wild-type and Omicron spike protein, as well as T-cell stimulation assays, were performed.

RESULTS:

High levels of SARS-CoV-2 anti-spike immunoglobulin G (IgG) antibodies were found in all participants. Anti-nucleocapsid IgG and Omicron-specific neutralizing antibodies increased in patients with rebound. Robust SARS-CoV-2-specific T-cell responses were observed, higher in rebound compared with early acute COVID-19 patients. Inflammatory markers mostly decreased during rebound. Two patients sampled longitudinally demonstrated an increase in activated cytokine-producing CD4+ T cells against viral proteins. No characteristic resistance mutations were identified. SARS-CoV-2 was isolated by culture from 1 of 8 rebound patients; Polybrene addition increased this to 5 of 8.

CONCLUSIONS:

Nirmatrelvir/ritonavir treatment does not impede adaptive immune responses to SARS-CoV-2. Clinical rebound corresponds to development of a robust antibody and T-cell immune response, arguing against a high risk of disease progression. The presence of infectious virus supports the need for isolation and assessment of longer treatment courses. Clinical trials registration. NCT04401436.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Topics: Long Covid / Variants Language: English Journal subject: Communicable Diseases Year: 2022 Document Type: Article Affiliation country: Cid

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Topics: Long Covid / Variants Language: English Journal subject: Communicable Diseases Year: 2022 Document Type: Article Affiliation country: Cid