Importance: The antiviral activity and efficacy of anti-SARS-CoV-2 monoclonal antibody (mAb) therapies to accelerate recovery from COVID-19 is important to define.
Objective: To determine safety and efficacy of the mAb bamlanivimab to reduce nasopharyngeal (NP) SARS-CoV-2 RNA levels and symptom duration.
Design: ACTIV-2/A5401 is a randomized, blinded, placebo-controlled platform trial. Two dose cohorts were enrolled between August 19 and November 17, 2020 for phase 2 evaluation: in the first, participants were randomized 1:1 to bamlanivimab 7000 mg versus placebo, and in the second to bamlanivimab 700 mg versus placebo. Randomization was stratified by time from symptom onset (≤ or >5 days) and risk of progression to severe COVID-19 ("higher" vs "lower").
Setting: Multicenter trial conducted at U.S. sites.
Participants: Non-hospitalized adults ≥18 years of age with positive SARS-CoV-2 antigen or nucleic acid test within 7 days, ≤10 days of COVID-19 symptoms, and with oxygen saturation ≥92% within 48 hours prior to study entry.
Intervention: Single infusion of bamlanivimab (7000 or 700 mg) or placebo.
Main Outcomes And Measures: Detection of NP SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28, time to improvement of all of 13 targeted COVID-19 symptoms by daily self-assessment through day 28, and grade 3 or higher treatment emergent adverse events (TEAEs) through day 28. Secondary measures included quantitative NP SARS-CoV-2 RNA, all-cause hospitalizations and deaths (composite), area under the curve of symptom scores from day 0 through day 28, plasma bamlanivimab concentrations, plasma and serum inflammatory biomarkers, and safety through week 24.
Results: Ninety-four participants were enrolled to the 7000 mg cohort and 223 to the 700 mg cohort and initiated study intervention. The proportion meeting protocol criteria for "higher" risk for COVID-19 progression was 42% and 51% for the 7000 and 700 mg cohort, respectively. Median time from symptom onset at study entry for both cohorts was 6 days. There was no difference in the proportion with undetectable NP SARS-CoV-2 RNA at any post-treatment timepoints (risk ratio compared to placebo, 0.82-1.05 for 7000 mg dose [overall p=0.88] and 0.81-1.21 for 700 mg dose [overall p=0.49]), time to symptom improvement (median of 21 vs 18.5 days, p=0.97, for 7000 mg bamlanivimab vs placebo and 24 vs 20.5 days, p=0.08, for 700 mg bamlanivimab vs placebo), or grade 3+ TEAEs with either dose compared to placebo. Median NP SARS-CoV-2 RNA levels were lower at day 3 and C-reactive protein, ferritin, and fibrinogen levels significantly reduced at days 7 and 14 for bamlanivimab 700 mg compared to placebo, with similar trends observed for bamlanivimab 7000 mg. Viral decay modeling supported more rapid decay with bamlanivimab compared to placebo.
Conclusions And Relevance: Treatment with bamlanivimab 7000 mg and 700 mg was safe and compared to placebo led to more rapid reductions in NP SARS-CoV-2 RNA and inflammatory biomarkers, but did not decrease time to symptom improvement. The clinical utility of mAbs for outcomes other than hospitalizations and deaths is uncertain.
Trial Registration: ClinicalTrials.gov Identifier: NCT04518410.
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http://dx.doi.org/10.1101/2021.12.17.21268009 | DOI Listing |
J Infect Dev Ctries
December 2024
Federal University of São João Del Rei, Dona Lindu Campus, Sebastião Gonçalves Coelho Street, 400, Chanadour, 35501-296 Divinópolis, MG, Brazil.
Introduction: We assessed the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated socio-occupational factors among delivery riders from a Brazilian city at two time points during the pandemic.
Methodology: Surveys for antibody and viral RNA testing were conducted from November 2020 to January 2021, and from March to May 2021 in a group of 117 delivery riders. A questionnaire on socio-occupational characteristics and coronavirus disease 2019 (COVID-19) preventive measures was completed.
Virol J
January 2025
Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong, 518118, China.
Background: SHEN26 (ATV014) is an oral RNA-dependent RNA polymerase (RdRp) inhibitor with potential anti-SARS-CoV-2 activity. Safety, tolerability, and pharmacokinetic characteristics were verified in a Phase I study. This phase II study aimed to verify the efficacy and safety of SHEN26 in COVID-19 patients.
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January 2025
Department of Bioengineering, Faculty of engineering, Integral University, Lucknow-226026, India. Electronic address:
Globally, over 768 million confirmed cases and 6.9 million deaths had been documented as of July 17, 2023. Coronaviruses have a relatively large RNA genome.
View Article and Find Full Text PDFEBioMedicine
January 2025
Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, New Cornerstone Science Foundation, Beijing, 100084, China. Electronic address:
Background: The widespread and evolution of RNA viruses, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the importance of fast identification of virus subtypes, particularly in non-laboratory settings. Rapid and inexpensive at-home testing of viral nucleic acids with single-base resolution remains a challenge.
Methods: Topologically constrained DNA ring is engineered as substrates for the trans-cleavage of Cas13a to yield an accelerated post isothermal amplification.
Viruses
January 2025
1st Department of Internal Medicine, Laiko General Hospital, 11527 Athens, Greece.
Background: Cognitive function decline is a problem in aging people living with HIV (PLWHIV). COVID-19 infection is associated with neuropsychiatric manifestations that may persist. The aim of our study was to evaluate cognitive function in PLWHIV before and after COVID-19 infection.
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