Bamlanivimab as monotherapy in two immunocompromised patients with COVID-19.
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ABSTRACT:
SUBMITTER: Destras G
PROVIDER: S-EPMC8318407 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Since the beginning of vaccination programs against COVID-19 in different countries, several populations such as patients with specific immunological conditions have been considered as the priorities for immunization. In this regard, patients with autoimmune diseases or those receiving immunosuppressive agents and anti-cancer therapies, need special attention. However, no confirmed data is presently available regarding COVID-19 vaccines in these populations due to exclusion from the conducted clinical trials. Given the probable suppression or over-activation of the immune system in such patients, reaching a consensus for their vaccination is critical, besides gathering data and conducting trials, which could probably clarify this matter in the future. In this review, besides a brief on the available COVID-19 vaccines, considerations and available knowledge about administering similar vaccines in patients with cancer, hematopoietic stem cell transplantation, solid organ transplantation, multiple sclerosis (MS), inflammatory bowel disease (IBD), and rheumatologic and dermatologic autoimmune disorders are summarized to help in decision making. As discussed, live-attenuated viruses, which should be avoided in these groups, are not employed in the present COVID-19 vaccines. Thus, the main concern regarding efficacy could be met using a potent COVID-19 vaccine. Moreover, the vaccination timing for maximum efficacy could be decided according to the patient's condition, indicated medications, and the guides provided here. Post-vaccination monitoring is also advised to ensure an adequate immune response. Further studies in this area are urgently warranted.
| S-EPMC8316069 | biostudies-literature
Project description:ImportanceCoronavirus disease 2019 (COVID-19) continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19.ObjectiveTo determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19.Design, setting, and participantsThe BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N = 613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebo were enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020.InterventionsPatients were randomized to receive a single infusion of bamlanivimab (700 mg [n = 101], 2800 mg [n = 107], or 7000 mg [n = 101]), the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab [n = 112]), or placebo (n = 156).Main outcomes and measuresThe primary end point was change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19-related hospitalization, an emergency department [ED] visit, or death at day 29).ResultsAmong the 577 patients who were randomized and received an infusion (mean age, 44.7 [SD, 15.7] years; 315 [54.6%] women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was -3.72 for 700 mg, -4.08 for 2800 mg, -3.49 for 7000 mg, -4.37 for combination treatment, and -3.80 for placebo. Compared with placebo, the differences in the change in log viral load at day 11 were 0.09 (95% CI, -0.35 to 0.52; P = .69) for 700 mg, -0.27 (95% CI, -0.71 to 0.16; P = .21) for 2800 mg, 0.31 (95% CI, -0.13 to 0.76; P = .16) for 7000 mg, and -0.57 (95% CI, -1.00 to -0.14; P = .01) for combination treatment. Among the secondary outcome measures, differences between each treatment group vs the placebo group were statistically significant for 10 of 84 end points. The proportion of patients with COVID-19-related hospitalizations or ED visits was 5.8% (9 events) for placebo, 1.0% (1 event) for 700 mg, 1.9% (2 events) for 2800 mg, 2.0% (2 events) for 7000 mg, and 0.9% (1 event) for combination treatment. Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment.Conclusions and relevanceAmong nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; no significant difference in viral load reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary end point.Trial registrationClinicalTrials.gov Identifier: NCT04427501.
| S-EPMC7821080 | biostudies-literature
Project description:The COVID-19 pandemic has disproportionately impacted immunocompromised patients. This diverse group is at increased risk for impaired vaccine responses, progression to severe disease, prolonged hospitalizations and deaths. At particular risk are people with deficiencies in lymphocyte number or function such as transplant recipients and those with hematologic malignancies. Such patients' immune responses to vaccination and infection are frequently impaired leaving them more vulnerable to prolonged high viral loads and severe complications of COVID-19. Those in turn, have implications for disease progression and persistence, development of immune escape variants and transmission of infection. Data to guide vaccination and treatment approaches in immunocompromised people are generally lacking and extrapolated from other populations. The large clinical trials leading to authorisation and approval of SARS-CoV-2 vaccines and therapeutics included very few immunocompromised participants. While experience is accumulating, studies focused on the special circumstances of immunocompromised patients are needed to inform prevention and treatment approaches.
| S-EPMC10091856 | biostudies-literature
Project description:BackgroundPatients with underlying medical conditions are at increased risk for severe coronavirus disease 2019 (Covid-19). Whereas vaccine-derived immunity develops over time, neutralizing monoclonal-antibody treatment provides immediate, passive immunity and may limit disease progression and complications.MethodsIn this phase 3 trial, we randomly assigned, in a 1:1 ratio, a cohort of ambulatory patients with mild or moderate Covid-19 who were at high risk for progression to severe disease to receive a single intravenous infusion of either a neutralizing monoclonal-antibody combination agent (2800 mg of bamlanivimab and 2800 mg of etesevimab, administered together) or placebo within 3 days after a laboratory diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The primary outcome was the overall clinical status of the patients, defined as Covid-19-related hospitalization or death from any cause by day 29.ResultsA total of 1035 patients underwent randomization and received an infusion of bamlanivimab-etesevimab or placebo. The mean (±SD) age of the patients was 53.8±16.8 years, and 52.0% were adolescent girls or women. By day 29, a total of 11 of 518 patients (2.1%) in the bamlanivimab-etesevimab group had a Covid-19-related hospitalization or death from any cause, as compared with 36 of 517 patients (7.0%) in the placebo group (absolute risk difference, -4.8 percentage points; 95% confidence interval [CI], -7.4 to -2.3; relative risk difference, 70%; P<0.001). No deaths occurred in the bamlanivimab-etesevimab group; in the placebo group, 10 deaths occurred, 9 of which were designated by the trial investigators as Covid-19-related. At day 7, a greater reduction from baseline in the log viral load was observed among patients who received bamlanivimab plus etesevimab than among those who received placebo (difference from placebo in the change from baseline, -1.20; 95% CI, -1.46 to -0.94; P<0.001).ConclusionsAmong high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of Covid-19-related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.).
| S-EPMC8314785 | biostudies-literature
Project description:AbstractThe coronavirus disease 2019 (COVID-19) pandemic poses a great threat to public health. Individuals who are immunocompromised because of the progression of the primary disease or receiving immunosuppressive medications are prone to severe COVID-19 complications and poor outcomes. Abundant data have shown that many COVID-19 vaccines are safe and effective in large-scale populations; however, these clinical trials have excluded immunocompromised populations. Available evidence indicates that immunocompromised populations have a blunted immune response to other vaccines, raising concerns regarding the efficacy of COVID-19 vaccination in these populations. Thus, there is an urgent need to delineate the efficacy of COVID-19 vaccines in these vulnerable populations. Here, we review the characteristics of specific humoral and cellular responses to COVID-19 vaccination in immunocompromised populations, including HIV-infected patients and those receiving immunosuppressive treatment, especially solid organ transplant recipients and those undergoing anti-CD20 treatment. We also addressed the challenges that immunocompromised populations will face in the future pandemic and the need for basic and clinical translational studies to highlight the best vaccination strategies for these populations.
| S-EPMC9945070 | biostudies-literature
Project description:BackgroundNeutralizing monoclonal antibodies (mAbs) to SARS-CoV-2 are clinically efficacious when administered early, decreasing hospitalization and mortality in patients with mild or moderate COVID-19. We investigated the effects of receiving mAbs (bamlanivimab alone and bamlanivimab and etesevimab together) after SARS-CoV-2 infection on the endogenous immune response.MethodsLongitudinal serum samples were collected from patients with mild or moderate COVID-19 in the BLAZE-1 trial who received placebo (n=153), bamlanivimab alone [700 mg (n=100), 2800 mg (n=106), or 7000 mg (n=98)], or bamlanivimab (2800 mg) and etesevimab (2800 mg) together (n=111). A multiplex Luminex serology assay measured antibody titers against SARS-CoV-2 antigens, including SARS-CoV-2 protein variants that evade bamlanivimab or etesevimab binding, and SARS-CoV-2 pseudovirus neutralization assays were performed.ResultsThe antibody response in patients who received placebo or mAbs had a broad specificity. Titer change from baseline against a receptor-binding domain mutant (Spike-RBD E484Q), as well as N-terminal domain (Spike-NTD) and nucleocapsid protein (NCP) epitopes were 1.4 to 4.1 fold lower at day 15-85 in mAb recipients compared with placebo. Neutralizing activity of day 29 sera from bamlanivimab monotherapy cohorts against both spike E484Q and beta variant (B.1.351) were slightly reduced compared with placebo (by a factor of 3.1, p=0.001, and 2.9, p=0.002, respectively). Early viral load correlated with the subsequent antibody titers of the native, unmodified humoral response (p<0.0001 at Day 15, 29, 60 and 85 for full-length spike).ConclusionsPatients with mild or moderate COVID-19 treated with mAbs develop a wide breadth of antigenic responses to SARS-CoV-2. Small reductions in titers and neutralizing activity, potentially due to a decrease in viral load following mAb treatment, suggest minimal impact of mAb treatment on the endogenous immune response.
| S-EPMC8697104 | biostudies-literature
Project description: Not available
| S-BSST416 | biostudies-other
Project description:Therapeutics for patients hospitalized with coronavirus disease 2019 (COVID-19) are urgently needed during the pandemic. Bamlanivimab is a potent neutralizing monoclonal antibody that blocks severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) attachment and entry into human cells, which could potentially lead to therapeutic benefit. J2W-MC-PYAA was a randomized, double-blind, sponsor unblinded, placebo-controlled, single ascending dose first-in-human trial (NCT04411628) in hospitalized patients with COVID-19. A total of 24 patients received either placebo or a single dose of bamlanivimab (700 mg, 2,800 mg, or 7,000 mg). The primary objective was assessment of safety and tolerability, including adverse events and serious adverse events, with secondary objectives of pharmacokinetic (PK) and pharmacodynamic analyses. Treatment-emergent adverse event (TEAE) rates were identical in the placebo and pooled bamlanivimab groups (66.7%). There were no apparent dose-related increases in the number or severity of TEAEs. There were no serious adverse events or deaths during the study, and no discontinuations due to adverse events. PKs of bamlanivimab is linear and exposure increased proportionally with dose following single i.v. administration. The half-life was ~ 17 days. These results demonstrate the favorable safety profile of bamlanivimab, and provided the initial critical evaluation of safety, tolerability, and PKs in support of the development of bamlanivimab in several ongoing clinical trials.
| S-EPMC8653186 | biostudies-literature
Project description:BackgroundMonoclonal antibodies (mAb) have been introduced as a promising new therapeutic approach against SARS-CoV-2. At present, there is little experience regarding their clinical effects in patient populations underrepresented in clinical trials, e.g. immunocompromised patients. Additionally, it is not well known to what extent SARS-CoV-2 treatment with monoclonal antibodies could trigger the selection of immune escape viral variants.MethodsAfter identifying immunocompromised patients with viral rebound under treatment with bamlanivimab, we characterized the SARS-CoV-2-isolates by whole genome sequencing. Viral load measurements and sequence analysis were performed consecutively before and after bamlanivimab administration.FindingsAfter initial decrease of viral load, viral clearance was not achieved in five of six immunocompromised patients treated with bamlanivimab. Instead, viral replication increased again over the course of the following one to two weeks. In these five patients, the E484K substitution - known to confer immune escape - was detected at the time of viral rebound but not before bamlanivimab treatment.InterpretationTreatment of SARS-CoV-2 with bamlanivimab in immunocompromised patients results in the rapid development of immune escape variants in a significant proportion of cases. Given that the E484K mutation can hamper natural immunity, the effectiveness of vaccination as well as antibody-based therapies, these findings may have important implications not only for individual treatment decisions but may also pose a risk to general prevention and treatment strategies.FundingAll authors are employed and all expenses covered by governmental, federal state, or other publicly funded institutions.
| S-EPMC8278033 | biostudies-literature
Project description: Not available
| S-EPMC8233547 | biostudies-literature