BACKGROUND
It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic COVID-19 patients, is also effective in preventing the progression of severe disease and mortality following SARS-CoV-2 Delta variant infection.


METHODS
Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from October 1st 2021 - December 11th 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data. We used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization.


RESULTS
Of 10,036 patients with SARS-CoV-2 infection, 522 receiving sotrovimab were matched to 1,563 not receiving mAbs. Compared to mAb-untreated patients, sotrovimab treatment was associated with a 63% decrease in the odds of all-cause hospitalization (raw rate 2.1% versus 5.7%; adjusted OR 0.37, 95% CI 0.19-0.66) and an 89% decrease in the odds of all-cause 28-day mortality (raw rate 0% versus 1.0%; adjusted OR 0.11, 95% CI 0.0-0.79), and may reduce respiratory disease severity among those hospitalized.


CONCLUSION
Real-world evidence demonstrated sotrovimab effectiveness in reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Delta variant phase.

Real World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11–RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.

/pdf/screening-of-potent-neutralizing-antibodies-against-sars-cov-33wf253lzz.pdf

Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries

Background: Sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic COVID-19 patients, was effective in preventing the progression of severe disease and mortality following SARS-CoV-2 Delta variant infection. It is not known whether sotrovimab is similarly effective for SARS-CoV-2 Omicron variant infection. Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from December 26, 2021 to March 10, 2022 (>96% Omicron BA.1 variant), using electronic health records from a statewide health system linked to state-level vaccine and mortality data. We used propensity matching to select up to 3 patients not receiving mAbs or other authorized antivirals for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality. To evaluate change in sotrovimab effectiveness during the Omicron phase, we propensity matched sotrovimab-treated patients from Omicron to Delta (October 1-December 11, 2021) phases to each other and then to untreated controls with a treatment-variant interaction added to the logistic regression model. Results: Of 30,247 patients with SARS-CoV-2 infection, we matched 1,542 receiving sotrovimab to 3,663 not receiving treatment. Compared to untreated patients, sotrovimab treatment was not associated with reduced odds of all-cause 28-day hospitalization (raw rate 2.5% versus 3.2%; adjusted OR 0.82, 95% CI 0.55, 1.19) or mortality (raw rate 0.1% versus 0.2%; adjusted OR 0.62, 95% CI 0.07, 2.78). In the combined analysis across Omicron and Delta phases, the observed treatment OR was higher during Omicron than during Delta (OR 0.85 vs. 0.39, respectively; interaction p=0.053) Conclusion: Real-world evidence demonstrated sotrovimab was not associated with reduced hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Omicron BA.1 phase and attenuated compared to the Delta phase

Change in Effectiveness of Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients During the Omicron Phase

Background: Monoclonal antibody (mAb) treatment for COVID-19 has been underutilized due to logistical challenges, lack of access and variable treatment awareness among patients and providers. The use of telehealth during the pandemic provides an opportunity to increase access to COVID care. Methods: This is a single-center descriptive study of telehealth-based patient self-referral for mAb therapy between March 1, 2021 to October 31, 2021 at Baltimore Convention Center Field Hospital (BCCFH). Results: Among the 1001 self-referral patients, the mean age was 47, , and most were female (57%) white (66%), and had a primary care provider (62%). During the study period, self-referrals increased from 14 per month in March to 427 in October resulting in a 30-fold increase. About 57% of self-referred patients received a telehealth visit, and of those 82% of patients received mAb infusion therapy, either onsite or at other infusion sites. The median time from self-referral to onsite infusion was 2 days (1-3 IQR). Discussion: Our study shows the integration of telehealth with a self-referral process improved access to mAb infusion. A high proportion of self-referrals were appropriate and led to timely treatment. Incorporation of self-referral and telehealth for monoclonal antibody therapy led to successful timely infusions. This approach helped those without traditional avenues for care and avoided potential delay for patients seeking referral from their medical providers.

Feasibility of and Experience with Telehealth Based Patient Self-referral for COVID-19 Monoclonal Antibody Therapy

https://doi.org/10.1016/j.ijid.2022.10.002

Change in effectiveness of sotrovimab for preventing hospitalization and mortality for at-risk COVID-19 outpatients during an Omicron BA.1 and BA.1.1-predominant phase

ImportanceNeutralizing monoclonal antibody (MAB) therapies may benefit patients with mild to moderate COVID-19 at high risk for progressing to severe COVID-19 and/or hospitalization. Studies documenting approaches to deliver MAB infusions as well as demonstrating their efficacy are lacking. ObjectiveWe describe our experience and patient outcomes of almost 3,000 patients who received MAB infusion therapy at Northwell Health, a large integrated health care system in New York. Design, Setting, and ParticipantsThis is a descriptive study of adult patients who received MAB therapy between November 20, 2020, to January 31, 2021, and a retrospective cohort survival analysis comparing patients who received MAB therapy prior to admission versus those who did not. A multivariable Cox model with inverse probability weighting according to the propensity score including covariates (sociodemographic, comorbidities, and presenting vital signs) was used. Main outcomes and measuresThe primary outcome was in-hospital mortality; additional evaluations included ED utilization and hospitalization within 28 days of a positive COVID-19 test for patients who received MAB therapy. ResultsDuring the study period, 2818 adult patients received MAB infusion. Following therapy and within 28 days of COVID-19 test, 123 patients (4.4%) presented to the ED and were released and 145 patients (5.1%) were hospitalized. These 145 patients were compared with 200 controls who were eligible for but did not receive MAB therapy, and were hospitalized. In the MAB group, 16 (11%) patients met the primary outcome of in-hospital mortality, versus 21 (10.5%) in the control group. In an unadjusted Cox model, the hazard ratio (HR) for time to in-hospital mortality for the MAB group was 1.38 (95% confidence interval [95% CI] 0.696-2.719). Models adjusting for demographics (HR 1.1, 95% CI 0.53-2.23), demographics and Charlson Comorbidity Index (CCI) (HR 1.22, 95% CI 0.573-2.59), and with inverse probability weighting according to propensity scores (HR 1.19, 95% CI 0.619-2.29) did not demonstrate significance. The hospitalization rate was 4.4% for patients who received MAB therapy within 0-4 days, 5% within 5-7 days, and 6.1% within [≥]8 days of symptom onset (p-value = 0.15). Conclusions and relevanceEstablishing the capability to provide neutralizing MAB infusion therapy requires significant planning and coordination. While this therapy may be an important treatment option for early mild to moderate COVID-19 in high-risk patients, further investigations are needed to define the optimal timing of MAB treatment in order to reduce hospitalization and mortality.

https://www.medrxiv.org/content/medrxiv/early/2021/04/13/2021.04.09.21255219.full.pdf

Early Experience With Neutralizing Monoclonal Antibody Therapy For COVID-19

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Steve Bello

Author Tools

Chat about Author

Papers

Early Experience With Neutralizing Monoclonal Antibody Therapy For COVID-19