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.

Efficacy and safety of casirivimab and imdevimab for preventing and treating COVID-19: a systematic review and meta-analysis.

Background: The ongoing global epidemic of coronavirus disease 2019 (COVID-19) has created a serious public health problem. The selection of safe and effective therapeutic agents is of paramount importance. This systematic review aims to evaluate the efficacy and safety of the combination of casirivimab and imdevimab in the treatment of global cases of COVID-19. Methods: To identify randomized controlled trials (RCTs) investigating the combined administration of casirivimab and imdevimab for COVID-19 management, a comprehensive search was conducted across multiple databases including PubMed, Web of Science, Embase, and the Cochrane Library from their inception to September 10, 2022. Data on the efficacy and safety of casirivimab and imdevimab were extracted. Subgroup analyses and sensitivity analyses were performed. Results: A total of 851 articles were searched. Twelve studies were finally included in the meta-analysis, with 27,179 participants. Dichotomous and continuous variables were presented as odds ratios (ORs) and weighted mean differences (WMDs) with their 95% confidence intervals (CIs), respectively. Compared to placebo or alternative medications, the combination of casirivimab and imdevimab reduced viral load (WMD: -0.73, 95% CI: -1.09 to -0.38, P<0.01), all-cause mortality (OR =0.90, 95% CI: 0.82-0.99, P=0.03), the incidence of any serious adverse events (OR =0.80, 95% CI: 0.67-0.95, P=0.01), the incidence of Grade 3 or more severe adverse events (OR =0.76, 95% CI: 0.62-0.92, P=0.01), the likelihood of contracting COVID-19, the incidence of hospitalization, emergency room visits, and mortality (OR =0.54, 95% CI: 0.32-0.93, P=0.03). Conclusions: The monoclonal antibody combination of casirivimab and imdevimab is effective in treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as they can reduce viral load, all-cause mortality, infection rates, and the incidence of clinical outcomes of special interest after treatment, while maintaining a favorable safety profile.

Prophylactic antibodies inhibit spike-specific T and B cell responses after COVID-19 vaccination.

Active and passive immunization is used in high-risk patients to prevent severe courses of COVID-19, but the impact of prophylactic neutralizing antibodies on the immune reaction to the mRNA vaccines has remained enigmatic. Here we show that CD4 T and B cell responses to Spikevax booster immunization are suppressed by the therapeutic antibodies Casirivimab and Imdevimab. B cell and T cell responses were significantly induced in controls but not in antibody-treated patients. The data indicates that humoral immunity, i. e. high levels of antibodies, negatively impacts reactive immunity, resulting in blunted cellular responses upon boosting. This argues for temporal separation of vaccination efforts; with active vaccination preferably applied before prophylactic therapeutic antibody treatment.

Safety and Efficacy of SAB-185 for Non-hospitalized Adults with COVID-19: A Randomized Clinical Trial.

BACKGROUND: To address the need for novel COVID-19 therapies, we evaluated the fully-human polyclonal antibody product SAB-185 in a phase 3 clinical trial. METHODS: Non-hospitalized high-risk adults within 7 days of COVID-19 symptom onset were randomized 1:1 to open-label SAB-185 3,840 units/kg or casirivimab/imdevimab 1200 mg. Non-inferiority comparison was undertaken for the pre-Omicron population (casirivimab/imdevimab expected to be fully active) and superiority comparison for the Omicron population (casirivimab/imdevimab not expected to be active). Primary outcomes were the composite of all-cause hospitalizations/deaths and grade ≥3 treatment-emergent adverse events (TEAEs) through day 28. Secondary outcomes included time to sustained symptom improvement and resolution. RESULTS: Enrollment was terminated early due to low hospitalization/death rates upon Omicron emergence. 733 adults were randomized, 255 included in pre-Omicron and 392 in Omicron analysis populations. Hospitalizations/deaths occurred in 6 (5.0%) and 3 (2.2%) of pre-Omicron SAB-185 and casirivimab/imdevimab arms, respectively (absolute difference [95% CI] 2.7% [-2.3%, 8.6%]), inconclusive for non-inferiority; and 5 (2.5%) versus 3 (1.5%) (absolute difference 1.0% [-2.3%, 4.5%]) for Omicron. Risk ratios for grade ≥3 TEAEs were 0.94 [0.52, 1.71] (pre-Omicron) and 1.71 [0.96, 3.07] (Omicron). Time to symptom improvement and resolution were shorter for SAB-185, median 11 vs 14 (pre-Omicron) and 11 vs 13 days (Omicron) (symptom improvement), and 16 vs 24 days and 18 vs >25 days (symptom resolution), p<0.05 for symptom resolution for Omicron only. CONCLUSIONS: SAB-185 had an acceptable safety profile with faster symptom resolution in the Omicron population. Additional studies are needed to characterize its efficacy for COVID-19.

Successful use of tocilizumab and casirivimab/imdevimab in a twin pregnancy with critical COVID-19 - A case report.

COVID-19 in pregnancy is associated with increased maternal morbidity and mortality as well as higher risk for hospitalization in intensive care unit and mechanical ventilation. We present a 38-year-old 21+5week pregnant unvaccinated woman with twins and critical COVID-19 pneumonia caused by Delta SARS-CoV-2 strain. Because of rapid worsening of respiratory condition despite standard of care treatment with steroids, she received a combination of casirivimab/imdevimab and tocilizumab. After therapy we noticed respiratory improvement and after 10 days she was extubated. Due to selective fetal growth restriction of one of the twins, a planned caesarean section was performed at 34+6 weeks. Presented case indicates favorable outcome and safe use of casirivimab/imdevimab and tocilizumab in critical COVID-19, as no severe or minor signs or symptoms in the case presentation were observed neither in the mother nor in infants during the time of observation.

Unveiling therapeutic dynamics: An in-depth comparative analysis of neutralizing monoclonal antibodies and favipiravir in alleviating COVID-19 outpatients impacts among middle-aged and special populations (MA-FAST).

BACKGROUND: Neutralizing monoclonal antibodies (NMabs) are recognized for their efficacy against non-severe COVID-19. However, spike protein mutations may confer resistance. This study evaluates the effectiveness of favipiravir (FPV) versus NMabs in preventing severe COVID-19 in special populations. METHODS: A retrospective cohort was conducted on middle-aged, elderly, diabetic, or obese patients with COVID-19 treated with either FPV or NMabs. Propensity score matching (PSM) was used for analysis. RESULTS: The study included 1410 patients, resulting in four cohorts: middle-aged (36), elderly (48), diabetic (46), and obese (28) post-PSM. No significant differences were noted in 28-day emergency department (ED) visits across all groups between NMabs and FPV treatments, despite lower immunity in the FPV group. However, the diabetic group treated with FPV had higher 28-day hospitalization and oxygen supplemental, with no differences in the other groups. Intensive care unit (ICU) admissions, invasive mechanical ventilation, and mortality rates were similar between the two treatments. CONCLUSIONS: Early dose-adjusted FPV showed no difference from NMabs in preventing ED visits, ICU admissions, ventilator needs, or mortality among patients with major comorbidities. Diabetic patients on FPV experienced higher hospitalizations and oxygen needs, with no observed differences in other groups. FPV may be a viable alternative, especially in settings with limited resources.

Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia.

Introduction: Casirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm. Methods: This is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and ß-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality. Results: A total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data. Conclusion: The mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.

Clinical Efficacy of Imdevimab/Casirivimab for Persistent Omicron SARS-CoV-2 Infection in Patients with Hematological Malignancies.

Objective Prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been reported in immunocompromised patients, as they poorly develop antibodies against SARS-CoV-2. We conducted a clinical trial to determine the efficacy of Imdevimab/Casirivimab (Imde/Casiri), an anti-viral monoclonal antibody (mAb), for prolonged infection at our institution. Methods Nine patients with hematological malignancies (six with malignant lymphoma and three with multiple myeloma) in our institution presented with coronavirus disease 2019 caused by SARS-CoV-2 omicron variants (one, five, and one with BA.2, BA.5, and BF.7, respectively; two undetermined). Although not all nine patients developed severe disease, viral mRNA was detected in all patients after treatment with remdesivir or molnupiravir. Imde/casiri was infused 11-49 days after the disease onset. Results Within seven days of infusion, viral RNA was undetectable in five of the nine cases. Because all seven viruses isolated from patients whose viral RNA became undetectable showed low or no sensitivity to this monoclonal antibody cocktail, the disappearance of viral RNA in these cases may not be attributable to the antibody cocktail. Conclusion It may be worth considering the use of monoclonal antibodies that show some activity against these virus variants to treat persistent SARS-CoV-2 infection in immunocompromised patients.

Retrospective Case-Control Study of REGEN-COV (Casirivimab and Imdevimab) Therapy for Patients with COVID-19 and Cancer Using the United States MarketScan® Database.

INTRODUCTION: Patients with cancer may be at a higher risk of experiencing severe complications from coronavirus disease 2019 (COVID-19) than are patients without cancer. This study evaluated the efficacy of REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, for treating COVID-19 in patients with cancer in the USA. METHODS: Using the MarketScanⓇ database, de-identified data of patients with a COVID-19 diagnosis between November 1, 2020, and November 30, 2021, were analyzed. In the preliminary study, patients with COVID-19 were divided into two groups: those with and without cancer within 1 year prior to a COVID-19 diagnosis. In the main study, patients with COVID-19 with cancer were divided into two groups: those with and without REGEN-COV treatment. Patient outcomes, such as COVID-19-derived hospitalization, hospitalization duration, and medical costs, were assessed between these two groups by propensity score matching. RESULTS: Within the first 30 days of a COVID-19 diagnosis, the group treated with REGEN-COV had fewer hospitalizations (3.2% vs. 13.3%; p < 0.001), fewer mean hospitalization days (0.2 vs. 1.1 days; p < 0.001), and a lower mean-associated medical payment (2,709 vs. 8,120 USD; p < 0.001) than the group not treated with REGEN-COV. Patients with specific cancer types, including non-Hodgkin's lymphoma, leukemia, and lung cancer, had higher hospitalization rates than those with other cancer types. CONCLUSION: Patients with cancer treated with REGEN-COV experienced a decreased risk for hospitalization, hospitalization duration, and total COVID-19-related costs. Patients with cancer were at a higher risk of being hospitalized for COVID-19 than were those without cancer. The use of neutralizing antibody therapy may reduce the risk of severe COVID-19 infection for patients with cancer with an otherwise high risk. Future replication studies should be conducted using other databases that include Medicaid users and other insured persons for comparison and validation.

Neutralizing monoclonal antibodies for the prevention of severe COVID-19: a retrospective study during Omicron BA.1 variant surge.

Among treatment options for Coronavirus disease 2019 (COVID-19), monoclonal antibodies (mAbs) showed to be effective in preventing disease progression, but real-world data during the Omicron variant surge are still lacking. Multicentre retrospective study evaluating the effectiveness of sotrovimab and casirivimab-imdevimab in fragile patients with mild SARS-CoV-2 infection between November 2021 and March 2022. Unfavourable outcome was defined as increased need for oxygen supplementation and/or death. Of 268 study-participants, 12 (4.48%) previously needed supplemental oxygen, while 6 (2.24%) had active solid neoplasia (2.24%); 186 (69%) have previously received SARS-CoV-2 vaccination. Overall, 22 (8%) had unfavourable outcomes (42% versus 6% of patients with and without previous oxygen need and 50% versus 7% of patients with and without active solid neoplasia). Both supplemental oxygen therapy before SARS-CoV-2 infection and solid malignant tumour have shown to be risk factors for treatment failure. Log-rank test did not identify differences between sotrovimab and casirivimab-imdevimab treatment. Despite diffusion of Omicron variant, the rate of unfavourable outcome was higher than expected. The presence of underlying risk factors, including solid cancer and previous oxygen therapy are independently associated with risk of COVID-19 progression, suggesting the need for antiviral treatments not limited to mAbs and implementation of vaccine campaign.

Efficacy and safety of casirivimab-imdevimab combination on COVID-19 patients: A systematic review and meta-analysis randomized controlled trial.

Background: The advantages and disadvantages of casirivimab-imdevimab for coronavirus disease 2019 are not well understood. We conducted a systematic review and meta-analysis of relevant literature to determine the therapeutic effectiveness and potential side effects of casirivimab-imdevimab in COVID-19 patients. Methods: Databases were searched from the time of their commencement until February 28th, 2023. The primary results evaluated were the death rate at 28 days, progression of current clinical symptoms within 28 days, viral load, discharge from hospital, and any adverse events. Also, we contrasted the effects of the casirivimab-imdevimab treatment with placebo or standard of care. The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023412835). Results: A total of eight studies were included, comprising 19,819 patients, and conducted a qualitative assessment of their risk of bias using the Cochrane risk of bias tool. Casirivimab-imdevimab effectively reduced the mortality rate (OR = 0.62; 95 % CI of 0.40-0.98; p = 0.04; I2 = 30 %) and reduced the progression of clinical symptoms (OR = 0.86; 95 % CI of 0.79-0.93; p = 0.0003; I2 = 57 %). Casirivimab-imdevimab also improved viral load clearance and hospital discharge. Additionally, the trials' findings demonstrated a slight decrease in the likelihood of adverse events occurring with the use of casirivimab-imdevimab. Conclusion: Our research suggests that casirivimab-imdevimab may be a valuable, safe, and effective anti-SARS-CoV-2 regimen.

[Use of a combination of the virus-neutralizing monoclonal antibodies casirivimab and imdevimab for mild to moderate COVID-19 in patients at high risk of progression: Results of the non-interventional observational study].

AIM: To evaluate the efficacy and safety of a combination of virus-neutralizing monoclonal antibodies - MAB (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with risk factors in real word settings. MATERIALS AND METHODS: A non-interventional non-comparative observational study with primary prospective data collection included 108 patients with mild to moderate COVID-19 (mean age 61 years), who had risk factors for developing severe disease. All patients (n=108) were treated with a combination of MAB casirivimab and imdevimab intravenous single infusion 1200 mg (600 mg of each component). The efficacy and safety of MAB were assessed at 7, 14, and 28 days after infusion. RESULTS: Efficacy. Indications for hospitalization by day 7 from the moment of MAB administration were in 0.9% (n=1), by day 14 - in 1.9% (n=2), by day 28 - in 0.9% of patients; to stay in the intensive care units by the 7th day - in 4.6% (n=5), by the 14th day - in 0.9% (n=1), by the 28th day - in 0.9% (n=1) patients. During 28 days of follow up, the need for mechanical ventilation and extracorporeal membrane oxygenation was registered in 2/108 (1.8%) patients. There were no deaths directly related to COVID-19 in the assessed cohort of patients. Safety. By the 28th day of the follow up, no adverse effects due to MAB therapy were registered. CONCLUSION: An analysis of the results of a non-interventional observational study summarized in this article showed the high efficacy and safety of virus-neutralizing MAB combination (casirivimab and imdevimab) in patients with mild to moderate COVID-19 with of risk factors for severe COVID-19 in real word settings.

Comparing the efficacy of regen-cov, remdesivir, and favipiravir in reducing invasive mechanical ventilation need in hospitalized COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic stimulates research works to find a solution to this crisis from starting 2020 year up to now. With ending of the 2021-year, various advances in pharmacotherapy against COVID-19 have emerged. Regarding antiviral therapy, casirivimab and imdevimab antibody combination is a type of new immunotherapy against COVID-19. Standard antiviral therapy against COVID-19 includes Remdesivir and Favipiravir. AIM: To evaluate the efficacy of antibodies cocktail (casirivimab and imdevimab) compared to standard antiviral therapy in reducing the need for invasive mechanical ventilation (IMV). METHODS: 265 COVID-19 polymerase chain reaction confirmed patients with indication for antiviral therapy were included in this study and were divided into 3 groups (1: 2: 2): Group A: REGN3048-3051 antibodies cocktail (casirivimab and imdevimab), group B: Remdesivir, group C: Favipiravir. The study design is a single-blind non-randomized controlled trial Mansoura University Hospital owns the study's drugs. The duration of the study was about 6 mo after ethical approval. RESULTS: Casirivimab and imdevimab achieve less need for O2 therapy and IMV, with less duration of this need than remdesivir and favipiravir. CONCLUSION: Group A (casirivimab and imdevimab) achieve better clinical outcomes than groups B (remdesivir) and C (favipiravir) intervention groups.

Analysis of SARS-CoV-2 mutations associated with resistance to therapeutic monoclonal antibodies that emerge after treatment.

The mutation rate of the Omicron sublineage has led to baseline resistance against all previously authorized anti-Spike monoclonal antibodies (mAbs). Nevertheless, in case more antiviral mAbs will be authorized in the future, it is relevant to understand how frequently treatment-emergent resistance has emerged so far, under different combinations and in different patient subgroups. We report the results of a systematic review of the medical literature for case reports and case series for treatment-emergent immune escape, which is defined as emergence of a resistance-driving mutation in at least 20% of sequences in a given host at a given timepoint. We identified 32 publications detailing 216 cases that included different variants of concern (VOC) and found that the incidence of treatment emergent-resistance ranged from 10% to 50%. Most of the treatment-emergent resistance events occurred in immunocompromised patients. Interestingly, resistance also emerged against cocktails of two mAbs, albeit at lower frequencies. The heterogenous therapeutic management of those cases doesn't allow inferences about the clinical outcome in patients with treatment-emergent resistance. Furthermore, we noted a temporal correlation between the introduction of mAb therapies and a subsequent increase in SARS-CoV-2 sequences across the globe carrying mutations conferring resistance to that mAb, raising concern as to whether these had originated in mAb-treated individuals. Our findings confirm that treatment-emergent immune escape to anti-Spike mAbs represents a frequent and concerning phenomenon and suggests that these are associated with mAb use in immunosuppressed hosts.

Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients.

Coronavirus disease 2019 (COVID-19) caused a progress in research to find a solution to this pandemic. Also, various advances in pharmacotherapy against COVID-19 have emerged. Regarding antiviral therapy, casirivimab and imdevimab are antibodies combination against COVID-19. Standard antiviral therapy against COVID-19 includes remdesivir and favipiravir. The objectives were to compare progression and multi-organ function of hospitalized COVID-19 patients between these three antiviral groups. 265 COVID-19 hospitalized patients were included in this study and were divided into 3 groups (1:2:2), respectively, Group (A): casirivimab and imdevimab, group (B): remdesivir, and group (C): favipiravir. The design of the study is a single blind non-randomized controlled trial. This study is a phase IV clinical trial (post-marketing study). The duration of the study was about 6 months after receiving the ethical approval. Casirivimab and imdevimab achieved less case progression as presented by lower World Health Organization scale (P < 0.05 in comparing group A with B and C) and better multi-organ functions as presented by lower Sequential Organ Function Assessment score (P < 0.05 in comparing group A with B and C) than remdesivir and favipiravir. From all these results, it is concluded that Group A (casirivimab and imdevimab) produces better outcomes than B (remdesivir) and C (favipiravir) intervention groups.

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.

Real-world experience of monoclonal antibodies in mild-to-moderate COVID-19 patients at a tertiary care center.

Background: Neutralizing antibodies cocktail (casirivimab and imdevimab) has received emergency use authorization recommendation by Food and Drug Administration (FDA) and WHO for mild-to-moderate COVID-19 infection in specific high-risk groups. Antibodies cocktail has shown promising results in preventing progression to severe disease, but the real-world experience is still evolving. Herein, we present a retrospective analysis of 22 patients who were administered the antibodies cocktail between August 2021 and March 2022 at our tertiary care center. Methods: We conducted an observational retrospective analysis of clinicoradiological, inflammatory parameters, progression of the disease, and outcome among 22 mild and moderate COVID-19 patients treated with antibodies cocktail. Results: The mean age was 67.7 years (SD ± 18.3) and comprised of 13 males (59%), while 9 were females (40.9%). Nine (40.9%) patients were fully vaccinated with two doses, nine (40.9%) were partially vaccinated with one dose while four patients (18.2%) were unvaccinated, and the rest were unvaccinated. Diabetes and hypertension were the commonest comorbidities; hematological and solid organ malignancies were other comorbidities. Eight patients had radiological opacities consistent with COVID-19 pneumonia and had shown significant regression in four patients after the therapy. None of our patients required supplemental oxygen or progressed to severe acute respiratory distress syndrome. All patients were discharged in a stable condition within 6 days of the therapy. Conclusions: The neutralizing antibodies cocktail has shown encouraging results in our analysis in preventing progression to severe disease in patients with high-risk conditions.

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.

Clinical study to compare the efficacy and safety of casirivimab & imdevimab, remdesivir, and favipravir in hospitalized COVID-19 patients.

Background: Corona Virus disease - 2019 (COVID-19) disease induces scientific research to find a control to this pandemic from 2020 year up to now. Recently, various advances in pharmacotherapy against COVID-19 have emerged. Objectives: To compare the efficacy and safety of antibodies cocktail (casirivimab and imdevimab), Remdesivir, and Favipravir in the COVID-19 patients. Study design: This study is a single-blind non-Randomized Controlled Trial (non-RCT). The drugs of the study are prescribed by lectures on chest diseases, faculty of medicine-Mansoura University. The duration of the study is about six months after ethical approval.265 hospitalized COVID-19 patients were used to represent the COVID-19 population and were assigned into three groups in a ratio of (1:2:2) respectively, Group (A) received REGN3048-3051(Antibodies cocktail (casirivimab and imdevimab)), group (B) received remdesivir, and group (C) received favipravir. Results: Casirivimab and imdevimab achieve less 28-day mortality rate, and less mortality at hospital discharge than Remdesivir, and Favipravir. Conclusion: From all of these results, it is concluded that Group A (Casirivimab & imdevimab) achieves more favorable outcomes than B (Remdesivir) & C (Favipravir) intervention groups. Clinical trial registration: NCT05502081, 16/08/2022, Clinicaltrials.gov.

Clinical, virological, and operational aspects of a single-center Belgian experience with in-hospital infusions of casirivimab/imdevimab and sotrovimab for mild/moderate COVID-19.

OBJECTIVES: To describe the clinical and virological characteristics of COVID-19 patients treated in a hospital with casirivimab/imdevimab and sotrovimab between June 2021 and April 2022 and to report the logistics for administering these monoclonal antibodies (mAbs). METHODS: All COVID-19 adult patients treated with mAbs at CHU Charleroi (Belgium) were included. A multidisciplinary monoclonal antibodies team (MMT) was dedicated to identify eligible patients and coordinate the administration of mAbs in a temporary structure created within the hospital. RESULTS: A total of 69 COVID-19 patients were treated with casirivimab/imdevimab (11.6%) and sotrovimab (88.4%) within a median of 4 days of symptom onset, mainly during the Omicron B.1.1.529 period (71%); no severe adverse events occurred. Thirty-eight (55%) were outpatients, and among the 31 inpatients, 42% were nosocomial COVID-19. The median age was 65 years [IQR, 50-73], and 53.6% were male. The most common risk factors for progression to severe COVID-19 were immunosuppression (72.5%), arterial hypertension (60.9%) and age>65 years (47.8%). One fifth were SARS-CoV-2-unvaccinated patients. The median Belgian MASS score for patient prioritization was 6 [IQR, 4-8]. On Day 29, 10.5% of the outpatients were hospitalized, and 1.4% were admitted to an intensive care unit (ICU); there were no COVID-19-related deaths. General practitioners referred 19.4% of the outpatients. CONCLUSIONS: In our experience, mAbs were prescribed in very high-risk patients with no adverse events, few progressions to severe COVID-19, and no related deaths. Our MMT has improved coordination of COVID-19 treatment and contribute to enhance communication with primary care.