Background: The interdependencies of viral replication and the host immune response in patients with coronavirus disease 2019 (COVID-19) remain to be defined. We investigated the viral determinants of antibody response, the predictors of nonseroconversion, and the role of antibodies on viral dynamics.
Methods: This was a prospective study in patients hospitalized with COVID-19 that was microbiologically confirmed by real-time polymerase chain reaction (RT-PCR). Serial nasopharyngeal and oropharyngeal swabs and plasma samples were obtained for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies (total and S-IgG/N-IgG), respectively.
Results: Of 132 patients included, 99 (75%) showed positive antibody titers after a median (Q1-Q3) of 11 (8-14) days. The median (Q1-Q3) follow-up was 74.5 (63.0-87.0) days. In an adjusted linear regression model, time to seropositivity was inversely associated with peak log SARS-CoV-2 viral load ( = .009) and positively with time to viral clearance ( = .004). Adjusted predictors of S-IgG levels were time to viral clearance ( < .001), bilateral lung infiltrates on admission ( = .011), and the time-dependent SARS-CoV-2 RNA ( < .001) and SARS-CoV-2 RNA area under the curve ( = .001). Thirty-three (25%) patients showed undetectable antibody titers. Patients who did not seroconvert had higher cycle threshold values of RT-PCR (38.0 vs 28.0; < .001), had shorter time to viral clearance (3.0 vs 41.0; < .001), and were more likely to have SARS-CoV-2 only detected on fecal samples ( < .001). Nonseroconvertors had also lower levels of blood inflammatory biomarkers on admission and lower disease severity.
Conclusions: Viral replication determines the magnitude of antibody response to SARS-CoV-2, which, in turn, contributes to viral clearance. COVID-19 patients who do not seroconvert exhibit a differential virological and clinical profile.
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http://dx.doi.org/10.1093/ofid/ofab005 | DOI Listing |
Nature
January 2025
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
This study examines the origin and differentiation of stem-like CD8+ T cells that are essential for sustained T cell immunity in chronic viral infections and cancer and also play a key role in PD-1 directed immunotherapy. These PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells, also referred to as precursors of exhausted T cells, have a distinct program that allows them to adapt to chronic antigen stimulation. Using the mouse model of chronic LCMV infection we found that virus specific stem-like CD8+ T cells are generated early (day 5) during chronic infection suggesting that this crucial fate commitment occurs irrespective of infection outcome.
View Article and Find Full Text PDFBiotechnol J
January 2025
Drug Substance Development, Spark Therapeutics, Inc., Philadelphia, USA.
Adeno-associated virus (AAV) vectors have become a leading platform for gene delivery. A major portion of gene therapy currently in clinical trials are AAV-based for a wide range of diseases. A commonly used method for AAV production is by mammalian or insect cell culture, with or without added viruses to introduce needed genetic elements for AAV production.
View Article and Find Full Text PDFPediatr Infect Dis J
December 2024
Medical Directorate, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Introduction: Despite the generally mild course of COVID-19 in children, immunocompromised patients may experience complications or severe infection. This study reports the clinical outcomes of pediatric patients treated with nirmatrelvir and ritonavir (N/R) for SARS-CoV-2 infection.
Methods: We retrospectively reported the data of children with any immunodeficiency with COVID-19 who received N/R treatment between March 2022 and June 2023 at the Bambino Gesù Children's Hospital.
Viruses
November 2024
Department of Microbiology & Immunology, Stanford Medical School, Stanford University, Stanford, CA 94305, USA.
Cytomegaloviruses, species-specific members of the betaherpesviruses, encode an impressive array of immune evasion strategies committed to the manipulation of the host immune system enabling these viruses to remain for life in a stand-off with host innate and adaptive immune mechanisms. Even though they are species-restricted, cytomegaloviruses are distributed across a wide range of different mammalian species in which they cause systemic infection involving many different cell types. Regulated, or programmed cell death has a recognized potential to eliminate infected cells prior to completion of viral replication and release of progeny.
View Article and Find Full Text PDFMicroorganisms
December 2024
Department for Infectious Diseases, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
In sepsis, a balanced pro-inflammatory and anti-inflammatory response results in the bacterial clearance and resolution of inflammation, promoting clinical recovery and survival. Semaphorins, a large family of secreted and membrane-bound glycoproteins, are newly recognized biomarkers and therapeutic targets in immunological and neoplastic disorders. Although semaphorins might also be a crucial part of host defense responses to infection, their role in sepsis is yet to be determined.
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