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

Monoclonal antibody (mAb) treatment for COVID-19 is associated with improved clinical outcomes. However, there is limited information regarding the impact of treatment on symptoms and the prevalence of post-COVID Conditions (PCC). Understanding of the association between time to mAb infusion and the development of PCC is also limited.This longitudinal study was conducted among patients with COVID-19 who received mAb infusions at a Federally Qualified Health Center in San Diego, CA. A series of telephone interviews were conducted at baseline and follow-up (14 days and 28+ days). A comprehensive symptom inventory was completed and physical and mental health status were measured using PROMIS-29 and PHQ-2. Pearson's Chi-squared tests and independent two-sample t-tests were performed to test for association between time to mAb infusion and outcomes at follow-up. A Poisson regression model was used to analyze whether time to mAb infusion predicts risk of developing PCC.Participants (N = 411) were 53% female, ranged in age from 16 to 92 years (mean 50), and a majority (56%) were Latino/Hispanic. Cross-sectional findings revealed a high symptom burden at baseline (70% of patients had cough, 50% had fever, and 44% had headache). The prevalence of many symptoms decreased substantially by the final follow-up survey (29% of patients had cough, 3% had fever, and 28% had headache). Longitudinal findings indicated that 10 symptoms decreased in prevalence from baseline to final follow-up, 2 remained the same, and 14 increased. The severity of symptoms and most patient-reported physical and mental health measure scores decreased over time. The prevalence of PCC was 69% when PCC was defined as ≥ 1 symptom at final follow-up. Time to mAb infusion was not significantly associated with any outcome at follow-up. Time to infusion was not associated with PCC status at final follow-up in the crude or adjusted Poisson regression models.The prevalence of PCC was high among this patient population following COVID-19 mAb treatment. Time to mAb infusion did not predict the development of PCC. Further research in these areas is essential to answer urgent clinical questions about effective treatments of COVID-19. 

https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-023-08057-7

COVID-19 monoclonal antibody treatment impact on symptoms and post-COVID conditions among high-risk patients at a Federally Qualified Health Center

The US Food and Drug Administration has granted an emergency use authorization (EUA) for Eli Lilly and Company’s experimental monoclonal antibody treatment for COVID-19 The antibody, called bamlanivimab, neutralizes SARS-CoV-2 by binding to its spike protein and thereby preventing the virus from gaining a foothold into human cells “This is welcome news and supports growing evidence that potent neutralizing antibodies can benefit those in the early stages of infection,” Scripps Research scientist Dennis Burton says in an email Bamlanivimab is the first drug discovered during the pandemic to receive an EUA—every other treatment granted the status so far had been studied previously or approved for other diseases A Phase 2 study in people with mild or moderate COVID-19 found that the antibody reduced the amount of coronavirus detected in a nasopharyngeal swab In a result that scientists found puzzling, the effect was statistically significant only at the medium dose [ ]

FDA authorizes COVID-19 antibody therapy

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 Neutralizing monoclonal antibody (MAB) therapies may benefit patients with mild to moderate COVID-19 at high risk for progressing to severe COVID-19 or hospitalization. Studies documenting approaches to deliver MAB infusions and demonstrating their efficacy are lacking. Objective We describe our experience and the outcomes of almost 3000 patients who received MAB infusion therapy at Northwell Health, a large integrated health care system in New York. Methods This 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. The primary outcome was in-hospital mortality; additional evaluations included emergency department use and hospitalization within 28 days of a positive COVID-19 test for patients who received MAB therapy. Results During the study period, 2818 adult patients received MAB infusion. Following therapy and within 28 days of a COVID-19 test, 123 (4.4%) patients presented to the emergency department and were released, and 145 (5.1%) patients 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% CI 0.696-2.719). Models adjusting for demographics (HR 1.1, 95% CI 0.53-2.23), demographics and Charlson Comorbidity Index (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 to 4 days, 5% within 5 to 7 days, and 6.1% in ≥8 days of symptom onset (P=.15). Conclusions Establishing the capability to provide neutralizing MAB infusion therapy requires substantial planning and coordination. Although this therapy may be an important treatment option for early mild to moderate COVID-19 in patients who are at high risk, further investigations are needed to define the optimal timing of MAB treatment to reduce hospitalization and mortality.

Early Experience With Neutralizing Monoclonal Antibody Therapy for COVID-19: Retrospective Cohort Survival Analysis and Descriptive Study.

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

/pdf/authors-response-to-peer-reviews-of-early-experience-with-3hdlb4tb3r.pdf

Authors' Response to Peer Reviews of “Early Experience With Neutralizing Monoclonal Antibody Therapy for COVID-19: Retrospective Cohort Survival Analysis and Descriptive Study”

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Early Experience With Neutralizing Monoclonal Antibody Therapy for COVID-19: Retrospective Cohort Survival Analysis and Descriptive Study.

Early Experience With Neutralizing Monoclonal Antibody Therapy For COVID-19

Authors' Response to Peer Reviews of “Early Experience With Neutralizing Monoclonal Antibody Therapy for COVID-19: Retrospective Cohort Survival Analysis and Descriptive Study”