Evidence map›Paper›PMID 35303909›Full record

Trial reportJournal of translational medicine2022

Relationship between gene expression patterns from nasopharyngeal swabs and serum biomarkers in patients hospitalized with COVID-19, following treatment with the neutralizing monoclonal antibody bamlanivimab.

Jonathan T Sims, Josh Poorbaugh, Ching-Yun Chang, Timothy R Holzer, Lin Zhang, Sarah M Engle, Stephanie Beasley, Thompson N Doman, Lynn Naughton, Richard E Higgs and 2 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04411628 (A Randomized, Placebo-Controlled, Double-Blind, Sponsor Unblinded, Single Ascending Dose, Phase 1 First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous LY3819253 in Participants Hospitalized for COVID-19), which is not on this map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 26% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04411628 phase1completednot on this map

A Randomized, Placebo-Controlled, Double-Blind, Sponsor Unblinded, Single Ascending Dose, Phase 1 First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous LY3819253 in Participants Hospitalized for COVID-19

TypeinterventionalSponsorEli Lilly and CompanyRan2020 to 2020Enrolled26ConditionsCOVID-19ArmsLY3819253, Placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19.The Cochrane database of systematic reviews · 2022
    Pooled it
  2. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Jonathan T SimsEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Josh PoorbaughEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Ching-Yun ChangEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Timothy R HolzerEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Lin ZhangEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Sarah M EngleEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Stephanie BeasleyEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Thompson N DomanEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Lynn NaughtonEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Richard E HiggsEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Nicole KallewaardEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA.
Robert J BenschopEli Lilly and Company, Lilly Corporate Center, 893 S Delaware St., Indianapolis, IN, 46285, USA. rbenschop@lilly.com.ORCID 0000-0001-6313-5218
Eli Lilly (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA thorough understanding of a patient's inflammatory response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is crucial to discerning the associated, underlying immunological processes and to the selection and implementation of treatment strategies. Defining peripheral blood biomarkers relevant to SARS-CoV-2 infection is fundamental to detecting and monitoring this systemic disease. This safety-focused study aims to monitor and characterize the immune response to SARS-CoV-2 infection via analysis of peripheral blood and nasopharyngeal swab samples obtained from patients hospitalized with Coronavirus disease 2019 (COVID-19), in the presence or absence of bamlanivimab treatment.

methods23 patients hospitalized with COVID-19 were randomized to receive a single dose of the neutralizing monoclonal antibody, bamlanivimab (700 mg, 2800 mg or 7000 mg) or placebo, at study initiation (Clinical Trial; NCT04411628). Serum samples and nasopharyngeal swabs were collected at multiple time points over 1 month. A Proximity Extension Array was used to detect inflammatory profiles from protein biomarkers in the serum of hospitalized COVID-19 patients relative to age/sex-matched healthy controls. RNA sequencing was performed on nasopharyngeal swabs. A Luminex serology assay and Elecsys® Anti-SARS-CoV-2 immunoassay were used to detect endogenous antibody formation and to monitor seroconversion in each cohort over time. A mixed model for repeated measures approach was used to analyze changes in serology and serum proteins over time.

resultsLevels of IL-6, CXCL10, CXCL11, IFNγ and MCP-3 were > fourfold higher in the serum of patients with COVID-19 versus healthy controls and linked with observations of inflammatory and viral-induced interferon response genes detected in nasopharyngeal swab samples from the same patients. While IgA and IgM titers peaked around 7 days post-dose, IgG titers remained high, even after 28 days. Changes in biomarkers over time were not significantly different between the bamlanivimab and placebo groups.

conclusionsSimilarities observed between nasopharyngeal gene expression patterns and peripheral blood biomarker profiles reveal a connection between the circulation and processes in the nasopharyngeal cavity, reinforcing the potential utility of systemic blood biomarker profiling for therapeutic monitoring of patient response. Serological antibody responses in patients correlated closely with reductions in the COVID-19 inflammatory protein biomarker signature. Bamlanivimab did not affect the biomarker dynamics in this hospitalized patient population.

Indexed as

COVID-19 Drug TreatmentAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntibodies, ViralBiomarkersGene ExpressionHumansNasopharynxSARS-CoV-2Antibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntibodies, ViralbamlanivimabBiomarkersAnalytesBamlanivimabBiomarkersCOVID-19Gene expressionLuminexRNA-seq

Identifiers

PMID35303909
PMCPMC8931785
OpenAlexW4220791806

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.