Monoclonal Antibody Therapies Against SARS-CoV-2: Promises and Realities.

Monoclonal antibodies targeting the Spike protein of SARS-CoV-2 have been widely deployed in the ongoing COVID-19 pandemic. I review here the impact of those therapeutics in the early pandemic, ranging from structural classification to outcomes in clinical trials to in vitro and in vivo evidence of basal and treatment-emergent immune escape. Unfortunately, the Omicron variant of concern has completely reset all achievements so far in mAb therapy for COVID-19. Despite the intrinsic limitations of this strategy, future developments such as respiratory delivery of further engineered mAb cocktails could lead to improved outcomes.

Lung Ultrasound Is Useful for Evaluating Lung Damage in COVID-19 Patients Treated with Bamlanivimab and Etesevimab: A Single-Center Pilot Study.

Background and Objectives: COVID-19 induces massive systemic inflammation. Researchers have spent much time and effort finding an excellent and rapid image tool to evaluate COVID-19 patients. Since the pandemic's beginning, lung ultrasound (LUS) has been identified for this purpose. Monoclonal antibodies (mAb) were used to treat mild patients and prevent respiratory disease worsening. Materials and Methods: We evaluated 15 Caucasian patients with mild COVID-19 who did not require home oxygen, treated with Bamlanivimab and Etesevimab (Group 1). A molecular nose-throat swab test confirmed the diagnosis. All were office patients, and nobody was affected by respiratory failure. They were admitted to receive the single-day infusion of mAb treatment in agreement with the Italian Drug Agency (AIFA) rules for approval. LUS was performed before the drug administration (T0) and after three months (T1). We compared LUS at T1 in other outpatients who came for follow-up and were overlapping at the time of diagnosis for admittance criteria to receive mAb (Group 2). Results: Our COVID-19 outpatients reported no hospitalization in a follow-up visit after recovery. All patients became SARS-CoV-2 negative within one month since T0. LUS score at T0 was 8.23 ± 6.46. At T1 we found a significant decrease in Group 1 LUS score (5.18 ± 4.74; p < 0.05). We also found a significant decrease in the LUS score of Group 1 T1 compared to Group2 T1 (5.18 ± 4.74 vs 7.82 ± 5.21; p < 0.05). Conclusion: Early treatment of the SARS-CoV-2 virus effectively achieves a better recovery from disease and reduces lung involvement after three months as evaluated with LUS. Despite extrapolation to the general population may be done with caution, based on our data this ultrasound method is also effective for evaluating and following lung involvement in COVID-19 patients.

A Randomized, Placebo-Controlled Clinical Trial of Bamlanivimab and Etesevimab Together in High-Risk Ambulatory Patients With COVID-19 and Validation of the Prognostic Value of Persistently High Viral Load.

BACKGROUND: Based on interim analyses and modeling data, lower doses of bamlanivimab and etesevimab together (700/1400 mg) were investigated to determine optimal dose and expand availability of treatment. METHODS: This Phase 3 portion of the BLAZE-1 trial characterized the effect of bamlanivimab with etesevimab on overall patient clinical status and virologic outcomes in ambulatory patients ≥12 years old, with mild-to-moderate coronavirus disease 2019 (COVID-19), and ≥1 risk factor for progressing to severe COVID-19 and/or hospitalization. Bamlanivimab and etesevimab together (700/1400 mg) or placebo were infused intravenously within 3 days of patients' first positive COVID-19 test. RESULTS: In total, 769 patients were infused (median age [range]; 56.0 years [12, 93], 30.3% of patients ≥65 years of age and median duration of symptoms; 4 days). By day 29, 4/511 patients (0.8%) in the antibody treatment group had a COVID-19-related hospitalization or any-cause death, as compared with 15/258 patients (5.8%) in the placebo group (Δ[95% confidence interval {CI}] = -5.0 [-8.0, -2.1], P < .001). No deaths occurred in the bamlanivimab and etesevimab group compared with 4 deaths (all COVID-19-related) in the placebo group. Patients receiving antibody treatment had a greater mean reduction in viral load from baseline to Day 7 (Δ[95% CI] = -0.99 [-1.33, -.66], P < .0001) compared with those receiving placebo. Persistently high viral load at Day 7 correlated with COVID-19-related hospitalization or any-cause death by Day 29 in all BLAZE-1 cohorts investigated. CONCLUSIONS: These data support the use of bamlanivimab and etesevimab (700/1400 mg) for ambulatory patients at high risk for severe COVID-19. Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants will require continued monitoring to determine the applicability of this treatment. CLINICAL TRIALS REGISTRATION: NCT04427501.

Clinical efficacy of different monoclonal antibody regimens among non-hospitalised patients with mild to moderate COVID-19 at high risk for disease progression: a prospective cohort study.

This study aimed to compare the clinical progression of COVID-19 in high-risk outpatients treated with the monoclonal antibodies (mAb) bamlanivimab, bamlanivimab-etesevimab and casirivimab-imdevimab. This is an observational, multi-centre, prospective study conducted from 18 March to 15 July 2021 in eight Italian tertiary-care hospitals including mild-to-moderate COVID-19 outpatients receiving bamlanivimab (700 mg), bamlanivimab-etesevimab (700-1400 mg) or casirivimab-imdevimab (1200-1200 mg). All patients were at high risk of COVID-19 progression according to Italian Medicines Agency definitions. In a patient subgroup, SARS-CoV-2 variant and anti-SARS-CoV-2 serology were analysed at baseline. Factors associated with 28-day all-cause hospitalisation were identified using multivariable multilevel logistic regression (MMLR) and summarised with adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 635 outpatients received mAb: 161 (25.4%) bamlanivimab, 396 (62.4%) bamlanivimab-etesevimab and 78 (12.2%) casirivimab-imdevimab. Ninety-five (15%) patients received full or partial SARS-CoV-2 vaccination. The B.1.1.7 (Alpha) variant was detected in 99% of patients. Baseline serology showed no significant differences among the three mAb regimen groups. Twenty-eight-day all-cause hospitalisation was 11.3%, with a significantly higher proportion (p 0.001) in the bamlanivimab group (18.6%), compared to the bamlanivimab-etesevimab (10.1%) and casirivimab-imdevimab (2.6%) groups. On MMLR, aORs for 28-day all-cause hospitalisation were significantly lower in patients receiving bamlanivimab-etesevimab (aOR 0.51, 95% CI 0.30-0.88 p 0.015) and casirivimab-imdevimab (aOR 0.14, 95% CI 0.03-0.61, p 0.009) compared to those receiving bamlanivimab. No patients with a history of vaccination were hospitalised. The study suggests differences in clinical outcomes among the first available mAb regimens for treating high-risk COVID-19 outpatients. Randomised trials are needed to compare efficacy of mAb combination regimens in high-risk populations and according to circulating variants.

Neutralising antibody escape of SARS-CoV-2 spike protein: Risk assessment for antibody-based Covid-19 therapeutics and vaccines.

The Spike protein is the target of both antibody-based therapeutics (convalescent plasma, polyclonal serum, monoclonal antibodies) and vaccines. Mutations in Spike could affect efficacy of those treatments. Hence, monitoring of mutations is necessary to forecast and readapt the inventory of therapeutics. Different phylogenetic nomenclatures have been used for the currently circulating SARS-CoV-2 clades. The Spike protein has different hotspots of mutation and deletion, the most dangerous for immune escape being the ones within the receptor binding domain (RBD), such as K417N/T, N439K, L452R, Y453F, S477N, E484K, and N501Y. Convergent evolution has led to different combinations of mutations among different clades. In this review we focus on the main variants of concern, that is, the so-called UK (B.1.1.7), South African (B.1.351) and Brazilian (P.1) strains.

Safety of Intradialytic Bamlanivimab/Etesevimab Administration in Two COVID-19 Dialysis Outpatients.

Chronic hemodialysis patients are at high risk of severe COVID-19 disease and death related to the infection. Anti-spike monoclonal antibodies administration reduces risk of disease progression and hospitalization in high-risk subjects but no clear data on end-stage renal disease are available. We report 2 cases of Bamlanivimab/Etesevimab administration to two not hospitalized chronic hemodialysis patients with SARS-CoV2 infection. Since they are large molecules (human immunoglobulin G1) with molecular weight of 146,000 Da, administration was conducted during the second hour of the dialysis session with no adverse reaction. Conclusions: Intradialytic administration of Bamlanivimab/Etesevimab could be considered safe and may allow adequate clinical observation time without hospital-stay prolongation.

SARS-CoV-2 neutralizing antibodies for COVID-19: Outcomes for bamlanivimab versus bamlanivimab-etesevimab combination in a racially diverse cohort of patients with significant comorbidities.

WHAT IS KNOWN AND OBJECTIVE: Anti-spike monoclonal antibodies (MAB) including bamlanivimab (BAM) and bamlanivimab/etesevimab (BAM/E) have shown reduced hospitalization rates for non-severe coronavirus disease 2019 (COVID-19) in clinical trials. Recent data have provided real-world hospitalization rates for high-risk patients treated with BAM, however, data on a similar cohort treated with BAM/E are lacking. METHODS: This retrospective cohort study evaluated outpatients ≥18 years with laboratory-confirmed mild/moderate COVID-19 who received MAB from 1 December 2020 to 19 April 2021. Use of BAM monotherapy changed to BAM/E combination on 27 March 2021. Primary outcome was overall rate of COVID-19 related-hospitalization, including comparison of hospitalization rates between MAB-formulation groups. Secondary outcomes were 30-day mortality and length of stay (LOS). RESULTS AND DISCUSSION: The population included 643 patients (BAM and BAM/E); median age was 58 years, 43% were male, median BMI was 33 kg/m2 , and 24% self-identified as Black. Patients in the BAM/E combination group were significantly younger with higher median BMI and a longer time from symptom onset to infusion. The incidence of 30-day COVID-19 related hospitalization was similar between patients receiving either BAM or BAM/E combination (7.8% and 7.2%, respectively). WHAT IS NEW AND CONCLUSION: This study represents the first such publication of real-world BAM/E hospitalization outcomes. Hospitalization rates utilizing BAM/E were comparable to BAM in our real-world study.

Evolution of Anti-SARS-CoV-2 Therapeutic Antibodies.

Since the first COVID-19 reports back in December of 2019, this viral infection caused by SARS-CoV-2 has claimed millions of lives. To control the COVID-19 pandemic, the Food and Drug Administration (FDA) and/or European Agency of Medicines (EMA) have granted Emergency Use Authorization (EUA) to nine therapeutic antibodies. Nonetheless, the natural evolution of SARS-CoV-2 has generated numerous variants of concern (VOCs) that have challenged the efficacy of the EUA antibodies. Here, we review the most relevant characteristics of these therapeutic antibodies, including timeline of approval, neutralization profile against the VOCs, selection methods of their variable regions, somatic mutations, HCDR3 and LCDR3 features, isotype, Fc modifications used in the therapeutic format, and epitope recognized on the receptor-binding domain (RBD) of SARS-CoV-2. One of the conclusions of the review is that the EUA therapeutic antibodies that still retain efficacy against new VOCs bind an epitope formed by conserved residues that seem to be evolutionarily conserved as thus, critical for the RBD:hACE-2 interaction. The information reviewed here should help to design new and more efficacious antibodies to prevent and/or treat COVID-19, as well as other infectious diseases.

Emergence of SARS-COV-2 Spike Protein Escape Mutation Q493R after Treatment for COVID-19.

We report in vivo selection of a severe acute respiratory syndrome coronavirus 2 spike mutation (Q493R) conferring simultaneous resistance to bamlanivimab and etesivimab. This mutation was isolated from a patient who had coronavirus disease and was treated with these drugs.

Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab, in Chinese Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, First-in-Human Phase 1 Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479, or LY-CoV016), in healthy adults. This paper describes a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose increased from 2.5 to 50 mg/kg. The elimination half-life (t1/2) value did not differ among different dose cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.).

Efficacy and Safety of Low-Dose, Rapidly Infused Bamlanivimab and Etesevimab: Phase 3 BLAZE-1 Trial for Mild-to-Moderate COVID-19.

INTRODUCTION: The monoclonal antibody therapies bamlanivimab (BAM) + etesevimab (ETE) received emergency use authorization (EUA) from the US Food and Drug Administration (February 9, 2021) for treatment of mild-to-moderate COVID-19. The EUA of BAM + ETE was revoked (December 14, 2023) due to the high prevalence of BAM + ETE-resistant variants of SARS-CoV-2. Efficacy and safety of 700/1400 mg and 2800/2800 mg BAM + ETE are well established and published; however, efficacy and safety of 350/700 mg BAM + ETE have not been disclosed to date. METHODS: This portion of phase 3, BLAZE-1 trial (J2X-MC-PYAB) enrolled patients (between June 17, 2020 and April 9, 2021) with mild-to-moderate COVID-19 within 3 days of laboratory diagnosis of SARS-CoV-2 infection. In total, 354 patients with at least one risk factor for severe COVID-19 were enrolled, randomized (2:3), and infused with placebo (N = 141) or 350/700 mg BAM + ETE (N = 213), over ~ 8 min. Primary endpoint was to assess proportion of patients with persistently high SARS-CoV-2 viral load (PHVL) (log viral load > 5.27) 7 days after infusion. RESULTS: Patients were aged (mean) 53 years, 49.7% female, and 82.7% White. Seven days after drug infusion, 10.8% (95% confidence interval: 6.6, 15.0; p < 0.001) of BAM + ETE-treated patients and 34.8% (26.9, 42.6) of placebo-treated patients had PHVL, and the viral load change from baseline (least square mean [standard error]) was - 3.50 (0.15; p < 0.001) in BAM + ETE-treated patients versus - 2.51 (0.19) in placebo-treated patients. The majority of treatment-emergent adverse events were considered mild or moderate in severity (BAM + ETE: 6.6%; placebo: 14.2%). No deaths were reported. CONCLUSIONS: Consistent with previous studies, patients treated with BAM + ETE (350/700 mg) had a significantly lower proportion of PHVL and greater reduction in viral load compared with placebo. The overall safety profile is consistent with higher doses of BAM + ETE. Infusions of over ~ 8 min did not result in meaningful increase in incidence of TEAEs compared to higher doses of BAM + ETE administered over 30-60 min. TRIAL REGISTRATION: Clinical trial.gov identifier, NCT04427501.

Effect of Bamlanivimab as Monotherapy or in Combination with Etesevimab or Sotrovimab on Persistently High Viral Load in Patients with Mild-to-Moderate COVID-19: A Randomized, Phase 2 BLAZE-4 Trial.

INTRODUCTION: Treatment with monoclonal antibodies provides rapid, passive immunity and may stop COVID-19 disease progression. The study evaluated the effect of bamlanivimab (BAM) or BAM + etesevimab (ETE)/sotrovimab compared to placebo on SARS-CoV-2 viral load in patients with COVID-19. METHODS: The phase 2, randomized, single-dose study included patients aged between ≥ 18 and < 65 years, not hospitalized at the time of randomization, and had ≥ 1 mild or moderate COVID-19 symptoms. Study included arms 1-6 (placebo, BAM 175 mg + ETE 350 mg, BAM 700 mg + ETE 1400 mg, BAM 2800 mg + ETE 2800 mg, BAM 700 mg alone, and BAM 350 mg + ETE 700 mg, respectively), BAM 700 mg + ETE 700 mg unintentional dosing; and arms 7 and 8 (BAM 700 mg + sotrovimab 500 mg and placebo, respectively). The primary endpoint was proportion of patients with SARS-CoV-2 log viral load > 5.27 on day 7 (persistently high viral load [PHVL]) who received BAM or BAM + (ETE or sotrovimab). RESULTS: A total of 725 patients, mean age 39.6 years (range 18-75 years), 50.2% male were randomized and infused with study drug in arms 1-6; and a total 202 patients, mean age 38 years (range 18-63 years), 53.5% female were randomized and infused with study drug in arms 7 and 8. A significantly lower proportion of patients in arms 2-6 and arm 7 experienced PHVL on day 7 compared to placebo. On day 7, patients in arms 2, 3, and 6 consistently experienced significantly greater reduction in viral load than placebo. Significant improvement was observed in time to viral load clearance and time to symptom improvement by day 29 in some arms compared to placebo. No new safety concerns were observed with drug combinations. CONCLUSION: The study demonstrated that a significantly lower proportion of patients with mild-to-moderate COVID-19 treated with BAM or BAM + (ETE or sotrovimab) experienced a PHVL at day 7. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04634409.

Monoclonal antibody infusion reaction with bamlanivimab and etesevimab in a 5-year-old male with coronavirus disease 2019: a case report.

BACKGROUND: Bamlanivimab and etesevimab had been granted emergency use authorization in children under 12 years who are at risk of progression from mild/moderate coronavirus disease 2019 to severe disease and hospitalization. CASE REPORT: We report on a 5-year-old white male with preexisting conditions, predisposing him to severe disease, who developed hypoxia and flushing 3 minutes into his infusion, thus meeting the criteria for anaphylaxis. CONCLUSIONS: We believe this patient developed either an immunoglobulin E-mediated anaphylactic or a non-immunoglobulin E-mediated anaphylactoid reaction to bamlanivimab and etesevimab, which is an important possibility to consider on administration.

Effects of bamlanivimab alone or in combination with etesevimab on subsequent hospitalization and mortality in outpatients with COVID-19: a systematic review and meta-analysis.

Background: Coronavirus disease 2019 (COVID-19) has caused an enormous loss of life worldwide. The spike protein of the severe acute respiratory syndrome coronavirus 2 is the cause of its virulence. Bamlanivimab, a recombinant monoclonal antibody, has been used alone or in combination with etesevimab to provide passive immunity and improve clinical outcomes. A systematic review and meta-analysis was conducted to investigate the therapeutic effects of bamlanivimab with or without etesevimab (BAM/ETE) treatment. Methods: Our study was registered in PROSPERO (registry number CRD42021270206). We searched the following electronic databases, without language restrictions, until January 2023: PubMed, Embase, medRxiv, and the Cochrane database. A systematic review and meta-analysis was conducted based on the search results. Results: Eighteen publications with a total of 28,577 patients were identified. Non-hospitalized patients given bamlanivimab with or without etesevimab had a significantly lower risk of subsequent hospitalization (18 trials, odds ratio (OR): 0.37, 95% confidence interval (CI): [0.29-0.49], I2: 69%; p < 0.01) and mortality (15 trials, OR: 0.27, 95% CI [0.17-0.43], I2: 0%; p = 0.85). Bamlanivimab monotherapy also reduced the subsequent risk of hospitalization (16 trials, OR: 0.43, 95% CI [0.34-0.54], I2: 57%; p = 0.01) and mortality (14 trials, OR: 0.28, 95% CI [0.17-0.46], I2: 0%; p = 0.9). Adverse events from these medications were uncommon and tolerable. Conclusions: In this meta-analysis, we found the use of bamlanivimab with or without etesevimab contributed to a significantly-reduced risk of subsequent hospitalization and mortality in non-hospitalized COVID-19 patients. However, resistance to monoclonal antibodies was observed in COVID-19 variants, resulting in the halting of the clinical use of BAM/ETE. Clinicians' experiences with BAM/ETE indicate the importance of genomic surveillance. BAM/ETE may be repurposed as a potential component of a cocktail regimen in treating future COVID variants.

Neutralizing anti-spike monoclonal antibodies for COVID-19 in vulnerable populations: lessons learned and future directions.

INTRODUCTION: Anti-spike monoclonal antibodies were highly effective for prophylaxis and early treatment of mild-to-moderate COVID-19 in high-risk populations. AREAS COVERED: This article reviews the clinical trials that led to the emergency use authorization of bamlanivimab with or without etesevimab, casirivimab and imdevimab, sotrovimab, bebtelovimab, and tixagevimab and cilgavimab in the United States. Clinical trials provided evidence that anti-spike monoclonal antibodies were highly effective, if administered early, for the treatment of mild-to-moderate COVID-19 among high-risk patients. Clinical trials also provided evidence that certain anti-spike monoclonal antibodies were highly effective when given as pre-exposure or post-exposure prophylaxis among high-risk individuals, including immunosuppressed populations. The evolution of SARS-CoV-2 resulted in spike mutations that conferred reduced susceptibility to anti-spike monoclonal antibodies. EXPERT OPINION: Anti-spike monoclonal antibodies for treatment and prevention of COVID-19 resulted in therapeutic successes that resulted in reduced morbidity and improved survival among the high-risk populations. Lessons learned from their clinical use should guide the future development of durable antibody-based therapies. A strategy that will preserve their therapeutic lifespan is needed.

Pharmacokinetics, Efficacy, and Safety of a SARS-CoV-2 Antibody Treatment in Pediatric Participants: An Open-Label Addendum of a Placebo-Controlled, Randomized Phase 2/3 Trial.

INTRODUCTION: Bamlanivimab and etesevimab (BAM + ETE) are monoclonal antibodies (mAbs) effective in reducing COVID-19-related hospitalizations and all-cause mortality in adult participants at increased risk for severe disease. We present pharmacokinetic (PK), efficacy, and safety results from pediatric participants (< 18 years of age) with COVID-19 who were treated with BAM + ETE. METHODS: In an addendum to the phase 2/3 BLAZE-1 clinical trial (NCT04427501), pediatric participants received open-label weight-based dosing (WBD, n = 94) based on exposure-matching to the authorized dose of BAM + ETE in adult participants. For efficacy and safety assessments, placebo (n = 14) and BAM + ETE (n = 20)-treated adolescent participants (> 12 to < 18 years of age) from the BLAZE-1 trial were included in the overall pediatric population (N = 128). All participants had mild to moderate COVID-19 upon enrollment and ≥ 1 risk factor for severe COVID-19. The primary objective was to characterize the PK of BAM and ETE in the WBD population. RESULTS: The median age of the participants was 11.2 years, 46.1% were female, 57.9% were Black/African American, and 19.7% were Hispanic/Latino. The area under the curve for BAM and ETE in the WBD population was similar to that previously observed in adults. There were no COVID-19-related hospitalizations or deaths. All adverse events (AE) except one were mild or moderate, with one participant reporting a serious AE. CONCLUSION: WBD in pediatric participants achieved similar drug exposures compared to adult participants that received the authorized BAM + ETE dose. The pediatric efficacy and safety data were consistent with adults receiving mAbs for COVID-19. TRIAL REGISTRATION NUMBER: NCT04427501.

Evaluation of adverse events of bamlanivimab, bamlanivimab/etesevimab used for COVID-19 based on FAERS database.

BACKGROUND: We study the adverse events (AEs) of bamlanivimab (BAM), bamlanivimab/etesevimab (BAM/ETE) to alert risk factors during coronavirus disease 2019 (COVID-19) treatment and provide references for drug safety. RESEARCH DESIGN AND METHODS: Extract AEs from the COVID-19 Emergency Use Authorization (EUA) FDA Adverse Event Reporting System (FAERS) Public Dashboard. Disproportionality analysis was performed to discover the potential risks of BAM and BAM/ETE. RESULTS: With COVID-19 drugs as the research background, the number of BAM/ETE signals is about half that of BAM, and 80% of signals overlap with BAM. Signals such as atrial fibrillation, tachycardia, and confusional state are present in BAM but not in BAM/ETE. With BAM and BAM/ETE as the research background, potential safety signals of BAM/ETE such as acute respiratory failure, hypersensitivity, and infusion-related reaction require long-term observation, especially acute respiratory failure which is not in the label. CONCLUSIONS: The AEs report on this study confirm most of the label information of BAM and BAM/ETE. BAM/ETE is relatively safe, while the risk signals such as acute respiratory failure and infusion-related reaction require to be monitored.

Monoclonal Antibody Therapy for COVID-19: A Retrospective Observational Study at a Regional Hospital.

BACKGROUND: Monoclonal antibodies represent one option for treatment of COVID-19 early after infection. Although large clinical trials have been successfully conducted, real world data are needed to obtain a realistic assessment of the assumed effect on hospitalization rates. METHODS: For this retrospective, observational study, clinical data were collected in 2021 from outpatients (402) as well as hospitalized patients (350) receiving monoclonal antibodies Bamlanivimab, Casirivimab/Imdevimab or Etesevimab/Bamlanivimab. These data were compared with data from a control group of patients not receiving antibodies because admission to the hospital was too late for this therapy. RESULTS: Both groups showed a comparable spectrum of risk factors. Due to the late hospitalization of control patients, a higher frequency of severe symptoms, such as fever, dyspnea, syncope and lower viral load, were observed. CRP and leukocytes counts were also higher in the untreated group. Most importantly, hospitalization time was significantly shorter and the number of deaths was also lower in the treated group. CONCLUSIONS: Apparently, the application of anti-SARS-CoV-2 antibodies reduced the work load of our hospital as shown by the shorter hospitalization time and lower number of COVID-19-related deaths.

Monoclonal Antibody Use for Coronavirus Disease 2019 in Pediatric Patients: A Multicenter Retrospective Study.

Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died.

Low BAU/ml values with 4 of 5 SARS CoV-2 spike-specific monoclonal antibodies in the Roche Elecsys antibody assay.

BACKGROUND: The Abbott SARS-CoV-2 IgG Quant II assay and the Roche Elecsys double antigen sandwich (DAgS) immunoassay measure SARS-CoV-2 receptor binding domain (RBD)-specific antibodies in serum samples in different ways. The IgG Quant II assay uses an antigen in combination with a secondary antibody and the DAgS assay uses two antigens. The aim of the study was to investigate whether the assays give comparable results with monoclonal antibodies. MATERIAL AND METHODS: The immunoassays were tested with the RBD-specific human monoclonal antibodies (mAbs) casirivimab. imdevimab, CR3022, etesevimab and sotrovimab. The mAbs were tested at various concentrations in µg/ml, alone or in combination and the relative light units (RLU) and binding antibody units (BAU)/ml were determined. RESULTS: With 1 µg/ml of casirivimab, imdevimab, CR3022 and etesevimab the Abbott IgG II Quant assay yielded between 65 and 158 BAU/ml and the Elecsys assay < 0.4 - 7.1 BAU/ml. In the DAgS assay, the addition of a second and a third mAb increased the BAU/ml values synergistically. With increasing concentrations of the mAb combinations in µg/ml the Abbott IgG Quant II assay showed proportionate and the Elecsys DAgS assay disproportionate increases in BAU/ml. With 1 µg/ml sotrovimab the Abbott assay gave 39 and the Elecsys assay 136 BAU/ml. The DAgS assay showed a high dose hook effect in the µg/ml range. CONCLUSIONS: The secondary antibody-based and the DAgS-based SARS CoV-2 antibody assays gave very different results with 4 of 5 mAbs. This suggests that the two assays measure different binding characteristics. The ability of antibodies to cross-link multiple antigen-antibody complexes may contribute to the measurement signal in the DAgS assay.