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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: Our research suggests that casirivimab-imdevimab may be a valuable, safe, and effective anti-SARS-CoV-2 regimen.

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.

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.
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.
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.
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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: The neutralizing antibodies cocktail has shown encouraging results in our analysis in preventing progression to severe disease in patients with high-risk conditions.

Anti-spike monoclonal antibodies were highly effective for prophylaxis and early treatment of mild-to-moderate COVID-19 in high-risk populations.
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.
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.

The casirivimab and imdevimab antibody cocktail has proven to be extremely effective against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant. Currently, no data on the clinical outcomes of antibody cocktail with the newer omicron form is available. This retrospective study evaluated the effectiveness of casirivimab and imdevimab antibody cocktail in patients infected with SARS-CoV-2 delta and omicron variants.
Data of 85 patients of age < 60 years, with comorbid conditions and BMI > 25 kg/m2 were identified from a database of 871 patients.
Most of the patients in both delta and omicron groups were administered 600 mg casirivimab + 600 mg imdevimab intravenously. SARS-CoV-2 symptoms started resolving from the 3rd day and by the end of the 14th day most patients in both groups did not report any symptoms. There was no significant difference between delta and omicron group with respect to average symptom onset days, number of hospitalized days post cocktail and number of days post cocktail administration to reverse transcription polymerase chain reaction (RT-PCR) negative status. Forty (58%) patients in the delta group and 16 (94%) patients in the omicron group had the high-resolution computed tomography (HRCT) score of zero. No patient required oxygen support during hospitalization and no mortality was reported.
There was no difference in effectiveness and safety of casirivimab and imdevimab antibody cocktail in the patients infected with SARS-CoV-2 delta or omicron.

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.

OBJECTIVE: In this early retrospective cohort study, a total of 26 patients with SARS-CoV-2 were treated with bamlanivimab or casirivimab/imdevimab, and the reduction of the viral load associated with the developed clinical symptoms was analyzed.
METHODS: Patients in the intervention groups received bamlanivimab or casirivimab/imdevimab. Patients without treatment served as control. Outcomes were assessed by clinical symptoms and change in log viral load from baseline based on the cycle threshold over a period of 18 days.
RESULTS: Median log viral load decline was higher in both intervention groups after 3 and 6 days compared to control. However, at later time points, the decline of the viral load was more distinct in the control group. Mild symptoms of COVID-19 were observed in 6.3% of the intervention groups and in no patient of the control. No patients treated with bamlanivimab, 18.8% treated with casirivimab/imdevimab, and 14.2% in the control group developed moderate symptoms. Severe symptoms were recorded only in the control group (14.2%), including one related death.
CONCLUSIONS: Treatment with monoclonal SARS-CoV-2 antibodies seems to accelerate decline of virus loads, especially in the first 6 days after administration, compared to control. This may be associated with a reduced likeliness of a severe course of COVID-19.