bamlanivimab (LY-CoV555) / Eli Lilly, AbCellera, National Institute of Allergy and Infectious Diseases - LARVOL DELTA

SARS-CoV-2 spike mutations alter structure and energetics to modulate ACE2 binding immune evasion and viral adaptation. (PubMed, Sci Rep) - "E484K balances antibody evasion (e.g., against LY-CoV555) with receptor stabilization via compensatory interactions (e.g., K484-D38)...Our work provides the importance of real-time surveillance for mutations that exploit conformational flexibility or compensatory networks, informing the design of durable vaccines and multi-specific antibodies. These insights bridge molecular mechanisms with evolutionary dynamics, offering a framework to anticipate and counter emerging variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The pan-variant potential of light: 425 nm light inactivates SARS-CoV-2 variants of concern and non-cytotoxic doses reduce viral titers in human airway epithelial cells. (PubMed, mSphere) - "In this study, we show that visible light centered around 425 nm inactivates each of the five SARS-CoV-2 VOC lineages that have been identified by the World Health Organization (Alpha, Beta, Delta, Gamma, and Omicron) in cell-free suspensions in a dose-dependent manner, including bamlanivimab-resistant variants...Furthermore, visible light reduced the amount of virus produced in an infection model of the human airway at multiple stages of infection, demonstrating the antiviral capability of visible light. This study provides preclinical support for the development of visible light to serve as a SARS-CoV-2 countermeasure and warrants further investigation."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

CONDIVIDIAMO: COVID-19 and Disease Progression to the Severe Form: a Study on the Use of Monoclonal Antibodies Against SARS-CoV-2 (clinicaltrials.gov) - P=N/A | N=251 | Completed | Sponsor: University of Milano Bicocca | Recruiting ➔ Completed | N=1000 ➔ 251

Enrollment change • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Mutational Scanning and Binding Free Energy Computations of the SARS-CoV-2 Spike Complexes with Distinct Groups of Neutralizing Antibodies: Energetic Drivers of Convergent Evolution of Binding Affinity and Immune Escape Hotspots. (PubMed, Int J Mol Sci) - "In this study, we conducted a comprehensive structural and energetic analysis of SARS-CoV-2 spike receptor-binding domain (RBD) complexes with neutralizing antibodies from four distinct groups (A-D), including group A LY-CoV016, group B AZD8895 and REGN10933, group C LY-CoV555, and group D antibodies AZD1061, REGN10987, and LY-CoV1404...The results demonstrate excellent qualitative agreement between the predicted binding hotspots and the latest experiments on antibody escape. These findings provide valuable insights into the molecular determinants of antibody binding and viral escape, highlighting the importance of targeting conserved epitopes and leveraging combination therapies to mitigate the risk of immune evasion."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Monoclonal Antibodies in Prevention and Early Treatment of COVID-19 in Lung Transplant Recipients: A Systematic Review and Perspective on the Role of Monoclonal Antibodies in the Future. (PubMed, Transpl Int) - "Moreover, mAb therapy appeared safe and could be a viable option against other pathogens, a route that warrants further investigation. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=382133, identifier CRD42022382133."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Solid Organ Transplantation • Transplantation

Characterisation of the antibody-mediated selective pressure driving intra-host evolution of SARS-CoV-2 in prolonged infection. (PubMed, PLoS Pathog) - "One year later, the patient experienced clinically mild re-infection with Omicron BA.1.18, which was treated with sotrovimab and resulted in an increase in Omicron-reactive antibodies. In conclusion, the onset of an IgM-dominated endogenous immune response in an immunocompromised patient coincided with the appearance of additional mutations in the NTD and RBD of S in a bamlanivimab-resistant virus. Although virus elimination was ultimately achieved, this humoral immune response escaped detection by routine diagnosis and created a situation temporarily favouring the rapid emergence of various antibody escape mutants with known epidemiological relevance."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

COVID-ASSOCIATED ORGANIZING PNEUMONIA WITH CLAD IN A LUNG TRANSPLANT PATIENT (CHEST 2024) - "He tested positive for COVID 19 a week prior and was given intravenous bamlanivimab the previous day...Hyperkalemia was treated with sodium zirconium cyclosilicate...He was able to be discharged with home oxygen after completing five days of dexamethasone & remdesivir. He was planned for another five days of remdesivir followed by resumption of prednisone... Patients with post COVID pneumonia must be evaluated for organizing pneumonia in order to initiate early treatment. In addition, lung transplant patients who develop COVID infection must be monitored for decline in their lung function."

Clinical • Anemia • Cardiovascular • Chronic Kidney Disease • Cough • Fatigue • Hematological Disorders • Infectious Disease • Nephrology • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Thrombocytopenia • Transplantation

Identification of Antibody-Resistant SARS-CoV-2 Mutants via N4-Hydroxycytidine Mutagenesis. (PubMed, Antiviral Res) - "By inducing mutations with the active compound of Molnupiravir, N4-hydroxycytidine (NHC), and subsequently passaging the virus in the presence of antibodies, we identified specific Spike mutations linked to resistance...From a Wuhan-like strain of SARS-CoV-2, we identified the following mutations conferring strong resistance towards the corresponding antibodies: Bamlanivimab - E484K, F490S and S494P; Sotrovimab - E340K; Cilgavimab - K444R/E and N450D. From the Omicron B.1.1.529 variant, the strongly selected mutations were: Bebtelovimab - V445A; Sotrovimab - E340K and K356M; Cilgavimab - K444R, V445A and N450D...Notably, many of the identified resistance-conferring mutations are prevalent in real-world SARS-CoV-2 variants, but some of them (G485S, D428G, and K462E) have not yet been observed in circulating strains. Our approach offers a strategy for predicting the therapeutic efficacy of antibodies against emerging virus variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Impact of SARS-CoV-2 Resistance to Antiviral Monoclonal Antibody Therapy on Neutralizing Antibody Response. (PubMed, Pathog Immun) - P2/3 | "In this study, we assessed host neutralizing antibody (nAb) responses against both ancestral virus and those with treatment-emergent E484K bamlanivimab resistance mutations...Emerging drug resistance after SARS-CoV-2-specific mAb therapy led to a heightened host neutralizing antibody response to the mAb-resistant variant that was associated with eventual viral clearance. This demonstrates the interplay between the antiviral treatment-directed viral evolution and subsequent host immune response in viral clearance."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy and Safety of Low-Dose, Rapidly Infused Bamlanivimab and Etesevimab: Phase 3 BLAZE-1 Trial for Mild-to-Moderate COVID-19. (PubMed, Infect Dis Ther) - P2/3 | "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."

Journal • P3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Comparison Study of the Bio-Plex and Meso Scale Multiplexed SARS-CoV-2 Serology Assays Reveals Evidence of Diminished Host Antibody Responses to SARS-CoV-2 after Monoclonal Antibody Treatment. (PubMed, Pathog Immun) - "Assessment of immune responses in the four individuals treated with the 700 mg of bamlanivimab with emerging mAb resistance demonstrated a stronger anti-N IgG response (MSD) at day 28 (median 2.18 log BAU/mL) compared to participants treated with bamlanivimab who did not develop resistance (median 1.55 log BAU/mL). These data demonstrate the utility in using multiplex immunoassays for characterizing the immune responses with and without treatment in a study population and provide evidence that monoclonal antibody treatment in acute COVID-19 may have a modest negative impact on development of host IgG responses."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Monoclonal Antibody Therapies Against SARS-CoV-2: Promises and Realities. (PubMed, Curr Top Microbiol Immunol) - "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."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effective Treatment of COVID-19 Infection with Repurposed Drugs: Case Reports. (PubMed, Viral Immunol) - "Successful administration of multidrug therapy, such as combinations of hydroxychloroquine and azithromycin, doxycycline and ivermectin, or ivermectin, doxycycline, and azithromycin, has been reported. Multidrug therapy is effective because of the differing mechanisms of action of these drugs, and it may also mitigate the emergence of drug-resistant SARS-CoV-2 strains. The medicines were lopinavir/ritonavir (Kaletra), bamlanivimab (monoclonal antibody), glycopyrrolate-formoterol (Bevespi), ciclesonide (Alvesco), famotidine (Pepcid), and diphenhydramine (Benadryl)."

Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

Longitudinal Importance of the Soluble Receptor for Advanced Glycation End-Products in Non-intubated Hospitalized Patients with COVID-19 Pneumonia. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "We studied two cohorts in randomized clinical trials of monoclonal antibody treatment for COVID-19 (bamlanivimab and tixagevimab/cilgavimab). The trajectory of sRAGE was not influenced by treatment assignment. Our results indicate that plasma sRAGE is a valuable prognostic marker in COVID-19 up to three days after initial hospital presentation."

Clinical • Journal • Metastases • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • AGER

SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback. (PubMed, J Infect Dis) - "Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific reduction in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating memory B cell responses to infection, and single mAb administration can continue to impact memory B cell responses to additional antigen exposures months later."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study. (PubMed, Lancet Microbe) - "Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment."

Biomarker • Clinical data • Journal • Chronic Kidney Disease • Infectious Disease • Inflammation • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • CRP • IL6

Biophysical principles predict fitness of SARS-CoV-2 variants. (PubMed, Proc Natl Acad Sci U S A) - "We developed a biophysical model that uses statistical mechanics to map the molecular phenotype space, characterized by dissociation constants of RBD to ACE2, LY-CoV016, LY-CoV555, REGN10987, and S309, onto an epistatic fitness landscape. Our study sheds light on the impact of specific mutations on viral fitness and delivers a tool for predicting the future epidemiological trajectory of previously unseen or emerging low-frequency variants. These insights offer not only greater understanding of viral evolution but also potentially aid in guiding public health decisions in the battle against COVID-19 and future pandemics."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Organizing Pneumonia With Surgical Pathology Positive for SARS-CoV2 a Year After Initial COVID-19 Diagnosis Despite Negative COVID-19 PCR From Nasal Swabs and Bronchial Alveolar Lavage in a Lymphopenic Cancer Patient (ATS 2024) - "He received monoclonal antibody, Bamlanivimab, with little improvement...Given symptoms, negative infectious work up including fungal markers and PET scan with new bilateral ground glass opacities (GGOs), he was started on prednisone 10mg daily for presumed long COVID-19...He tested COVID PCR negative multiple times and was treated for presumed pneumonia with Augmentin and Levofloxacin with minimal improvement in symptoms...While COVID PCR from a BAL has high sensitivity, the patient tested negative multiple times with the diagnosis ultimately made with immunohistochemical stains from biopsy. Steroids continue to be the treatment of choice for PCOP."

Clinical • Bone Marrow Transplantation • Cough • Follicular Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Transplantation

Comparison of bamlanivimab with or without etesevimab and casirivimab-imdevimab in clinical outcomes in patients with COVID-19: a systematic review and meta-analysis. (PubMed, J Chemother) - No abstract available

Clinical data • Journal • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease

Viral Kinetics Model of SARS-CoV-2 Infection Informs Drug Discovery, Clinical Dose, and Regimen Selection. (PubMed, Clin Pharmacol Ther) - "We found good agreement between model predictions and clinical viral load reduction observed with anti-replicative nirmatrelvir/ritonavir (Paxlovid®) and neutralizing biologics bamlanivimab and casirivimab/imdevimab (REGEN-COV®), building confidence in the modeling framework to inform a dose selection...By benchmarking to bamlanivimab predictions, we justified dose levels of 75, 225, and 600 mg ensovibep to be administered intravenously in a Phase 2 clinical investigation. Upon trial completion, we found model predictions to be in good agreement with the observed patient data. These results demonstrate the utility of this modeling framework to guide the development of novel antiviral therapeutics."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy and safety of bamlanivimab in patients with COVID-19: A systematic review and meta-analysis. (PubMed, World J Virol) - "Although the results suggest the efficacy and safety of bamlanivimab in COVID-19 patients, further research is required to confirm the efficacy of this drug for the current circulating SARS-CoV-2 variants."

Journal • Retrospective data • Review • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

HEALTH OUTCOMES IN PATIENTS WITH SICKLE CELL DISEASE WITH COVID-19 INFECTION IN NEWARK, NJ (ASPHO 2024) - "Out of patients receiving COVID treatment, 9.6% received Remdesivir, 7.4% received steroids with or without remdesivir, 3.2% received hydroxychloroquine, and 1.1% received bamlanivimab. Our data suggests that patients with SCD and COVID-19 did not have significant respiratory complications, but we observed an increase in VOE rates in these patients. Our data also suggests that most patients recovered spontaneously without the use of COVID-19 directed therapy. However, further examination of the long-term effects in these patients is warranted."

Clinical • HEOR • Genetic Disorders • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Pain • Respiratory Diseases • Sickle Cell Disease • Thrombosis

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. (PubMed, Infect Dis Ther) - P2 | "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."

Combination therapy • Journal • Monotherapy • P2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Failure of bamlanivimab with selection of E484K mutation in an allogeneic stem cell transplant recipient with nosocomial SARS-CoV-2 infection. (PubMed, Antivir Ther) - "We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab."

Journal • Bone Marrow Transplantation • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Transplantation

Developing of SARS-CoV-2 fusion protein expressed in E. coli Shuffle T7 for enhanced ELISA detection sensitivity - an integrated experimental and bioinformatic approach. (PubMed, J Biomol Struct Dyn) - "A molecular docking simulation was conducted to assess the binding affinity of CoV2-Pro with LY-COV555 (Bamlanivimab) monoclonal antibody...The CoV2-Pro interacted with SARS-CoV-2 antibodies, confirming the correct antigenic structure. We assert with confidence that CoV2-Pro is ideal for developing an ELISA assay for precise diagnosis and rigorous vaccine evaluation during the COVID-19 prevalence.Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases