Publications by authors named "Kara W Chew"
T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, we assessed samples for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered at high risk for progression to severe COVID-19.
View Article and Find Full Text PDFBackground: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for mild to moderate COVID-19.
Methods: This phase 2/3, double-blind, randomized (1:1) study assessed oral NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In testing the primary endpoint of COVID-19‒related hospitalization and all-cause deaths and key secondary endpoints including symptom duration and COVID-19‒related medical visits, Type I error was controlled with prespecified sequential testing and the Hochberg procedure.
Article Synopsis
- * It includes recommendations for using the anti-SARS-CoV-2 neutralizing antibody pemivibart as pre-exposure prophylaxis based on systematic review evidence.
- * The guidelines follow GRADE methodology for assessing evidence certainty and strength of recommendations, and pemivibart is included in the FDA's Emergency Use Authorization.
We explored viral and symptom rebound after COVID-19 amubarvimab/romlusevimab monoclonal antibody therapy vs placebo in the randomized ACTIV-2/A5401 trial. Participants underwent nasal SARS-CoV-2 PCR at study days 3, 7, 14, and 28. Viral rebound was defined as RNA ≥3 and ≥0.
View Article and Find Full Text PDFPathogenic changes in gut microbial composition precede the onset of HIV-1 infection in men who have sex with men (MSM). This process is associated with increased levels of systemic inflammatory biomarkers and risk for AIDS development. Using mediation analysis framework, in this report we link the effects of unprotected receptive intercourse among MSM prior to primary HIV-1 infection to higher levels of proinflammatory cytokines sCD14 and sCD163 in plasma and a significant decrease in the abundance of A.
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- A study investigated whether the monoclonal antibodies amubarvimab/romlusevimab could lower the risk of Long COVID in non-hospitalized high-risk adults treated soon after COVID-19 symptoms began.
- Results showed that while this treatment significantly reduced hospitalizations and deaths (4% vs. 13% in the placebo group), it did not decrease the incidence of Long COVID symptoms, with 16% of treated participants reporting Long COVID compared to 14% in the placebo group.
- The conclusion is that although amubarvimab/romlusevimab is effective for immediate COVID-19 outcomes, additional strategies are necessary to prevent Long COVID.
Background: Anti-SARS-CoV-2 monoclonal antibodies (mAbs) have played a key role as an anti-viral against SARS-CoV-2, but there is a potential for resistance to develop. The interplay between host antibody responses and the development of monoclonal antibody (mAb) resistance is a critical area of investigation. In this study, we assessed host neutralizing antibody (nAb) responses against both ancestral virus and those with treatment-emergent E484K bamlanivimab resistance mutations.
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- The study evaluates two different antibody detection assays (MSD and Bio-Plex Pro) for their effectiveness in measuring antibodies against SARS-CoV-2, focusing on various antibody types (IgG, IgM, IgA) and antigens (RBD, N).
- Results showed high concordance (90.5% for anti-RBD IgG and 87% for anti-N IgG) in determining sample status as positive or negative across the two assays, indicating they can reliably assess immune responses.
- The research also found that participants treated with the monoclonal antibody bamlanivimab showed reduced IgG responses compared to those given a placebo, suggesting the treatment affects immune response
Article Synopsis
- Therapeutic monoclonal antibodies (mAbs), specifically bamlanivimab targeting the SARS-CoV-2 spike protein, have been shown to alter the memory B cell (MBC) responses in individuals already infected with the virus.
- The treatment skewed MBCs to favor non-receptor binding domain (RBD) epitopes, resulting in a weaker affinity for RBD memory B cells compared to those who received a placebo.
- Even after mRNA COVID-19 vaccination, these changes persisted, indicating that mAb treatment can have lasting effects on immune memory and how the immune system recognizes specific viral epitopes.
Background: We evaluated the fully human polyclonal antibody product SAB-185 in a phase 3 trial for COVID-19.
Methods: Nonhospitalized high-risk adults within 7 days of symptom onset were randomized 1:1 to open-label SAB-185 3840 units/kg or casirivimab/imdevimab 1200 mg. Noninferiority comparison was undertaken for pre-Omicron population (casirivimab/imdevimab expected to be fully active) and superiority comparison for the Omicron population (casirivimab/imdevimab not expected to be active).
Background: Reliable biomarkers of coronavirus disease 2019 (COVID-19) outcomes are critically needed. We evaluated associations of spike antibody (Ab) and plasma nucleocapsid antigen (N Ag) with clinical outcomes in nonhospitalized persons with mild-to-moderate COVID-19.
Methods: Participants were nonhospitalized adults with mild-to-moderate COVID-19 enrolled in ACTIV-2 between January and July 2021 and randomized to placebo.
Article Synopsis
- Host metabolic issues, particularly in tryptophan metabolism, are linked to the severity of COVID-19 and long COVID symptoms.
- People with HIV also experience similar metabolic problems, raising questions about their risk for severe COVID-19 outcomes.
- Research on samples from people living with HIV indicates that certain metabolic changes may predict higher risks for severe COVID-19 and long COVID, suggesting a need for further study.
Article Synopsis
- Outpatient treatment of COVID-19 using subcutaneous monoclonal antibodies (mAbs) could simplify logistics compared to intravenous delivery.
- In a clinical trial with 211 participants, the BMS mAbs did not show significant benefits in symptom improvement or viral load reduction compared to placebo, despite being safe with fewer severe adverse events reported.
- The results suggest that subcutaneous administration of BMS mAbs may not be effective for low-risk COVID-19 patients, potentially due to how the body absorbs mAbs through this method.
Article Synopsis
- Monoclonal antibodies are an important treatment for COVID-19, and a study compared the effects of single vs. dual mAb treatments, specifically amubarvimab and romlusevimab.
- The study found that dual-active mAbs resulted in a quicker reduction of viral load in patients, though hospitalizations and death rates were similar between the two treatment types.
- Additionally, dual-active therapy showed a lower incidence of resistance mutations compared to single-active treatment.
Article Synopsis
- Emergency use authorization allowed several monoclonal antibody (mAb) therapies to treat mild-to-moderate COVID-19 in high-risk patients, targeting the virus's spike protein to prevent infection.
- While mAb therapy can reduce viral loads and hospitalization rates, cases of viral resistance have led to significant viral rebounds in some patients.
- Researchers developed models to explain these rebounds, suggesting that replenishing target cells is necessary, and variations in immune response may determine who experiences these significant rebounds.
Background: Developing countries experience limited access to HCV laboratory tests for different reasons. Providing near to real-time HCV testing and results especially to at-risk populations including those in rural settings for timely initiation to treatment is key. Within a rural Myanmar setting, we compared HCV diagnostic detection and quantification of the GeneXpert, and Advanced Biological Laboratories UltraGene-HCV assays against the gold standard and reference method Roche real-time HCV in Myanmar.
View Article and Find Full Text PDFTherapeutic anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been extensively studied in humans, but the impact on immune memory of mAb treatment during an ongoing immune response has remained unclear. Here, we evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes.
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- T cells play a crucial role in fighting off various viral infections, including SARS-CoV-2, which causes COVID-19.
- A study involving 95 unvaccinated participants showed that most developed SARS2-specific T cell responses within 6 days of symptoms, indicating their importance in the immune response.
- The research found that robust CD4 and CD8 T cell responses were linked to lower levels of the virus in the upper respiratory tract, highlighting their protective function even without considering antibody levels.
Background: With the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need.
Methods: Safety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.govNCT04518410).
Article Synopsis
- The study compared PCSK9 levels in individuals with co-existing HIV and hepatitis C (HIV/HCV) vs. those with HIV alone, finding that PCSK9 levels were higher in the HIV/HCV group but not significantly so (P = 0.06).
- Following direct-acting antiviral (DAA) therapy for HCV, PCSK9 levels significantly declined in the HIV/HCV group, reaching levels similar to the HIV alone group (P = 0.003 and P = 0.02).
- The drop in PCSK9 was associated with reductions in inflammatory markers, suggesting that elevated PCSK9 in HIV/HCV may be more related to inflammation rather than cholesterol levels.
The COVID-19 pandemic has led to over 760 million cases and 6.9 million deaths worldwide. To mitigate the loss of lives, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease.
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- The study analyzed the effectiveness of time to symptom resolution (TSR) as a measure in outpatient COVID-19 treatment trials, using data from the ACTIV-2/A5401 trial involving high-risk and standard-risk participants.
- Participants tracked 13 symptoms and overall health for 29 days to assess the correlation between the sustained resolution of targeted symptoms and broader health outcomes.
- Results showed a strong correlation between TSR and overall symptom improvement, supporting TSR as a viable endpoint for clinical trials, while emphasizing the need for a careful definition of symptom resolution duration to reduce the chance of symptom recurrence.