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.

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.

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.

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.

Outcomes of SARS-CoV-2 infection among lung transplant recipients: A single center retrospective study.

BACKGROUND: Lung transplant recipients (LTRs) are at increased risk for coronavirus disease 2019 (COVID-19)-associated complications. METHODS: We aimed to describe the outcomes of polymerase chain reaction-documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LTRs followed at our institution from March 2020 to July 2022. The primary outcome investigated was hospitalization or death from COVID-19-related symptoms within 28 days from diagnosis. RESULTS: Overall, 60 cases were included, of which 18 (30%) reached the primary outcome. Only one patient (2%) died. Anti-spike monoclonal antibodies (mAbs) were administered as early treatment in 36 patients (casirivimab/imdevimab = 2, sotrovimab = 31, and tixagevimab/cilgavimab = 3). Multivariate analysis revealed that age >60 years (p = .003; odds ratio [OR] 9.41; confidence interval [CI] 2.52-41.05) was associated with a higher risk for the primary outcome, while administration of mAbs as early treatment (p = .030; OR 0.23; CI 0.06-0.87) was associated with a lower risk. No effect of vaccination and SARS-CoV-2 variant was observed. Forced expiratory volume in 1 s and forced vital capacity values did not decrease among 37 patients who had spirometry performed 1 month after COVID-19. CONCLUSIONS: We observed a relatively low morbidity and mortality of COVID-19 in LTR. mAb administration was associated with a better outcome.

Monoclonal Antibody Treatment of Breakthrough COVID-19 in Fully Vaccinated Individuals with High-Risk Comorbidities.

BACKGROUND: Breakthrough coronavirus disease 2019 (COVID-19) may occur in fully vaccinated persons. METHODS: We assessed the clinical outcomes of breakthrough COVID-19 in fully vaccinated individuals. RESULTS: In this cohort of 1395 persons (mean age, 54.3 years; 60% female; median body mass index, 30.7) who developed breakthrough COVID- 19, there were 107 (7.7%) who required hospitalization by day 28. Hospitalization was significantly associated with the number of medical comorbidities. Antispike monoclonal antibody treatment was significantly associated with a lower risk of hospitalization (odds ratio, 0.227; 95% confidence interval, 0.128-0.403; P < .001). The number needed to treat (NNT) to prevent 1 hospitalization was 225 among the lowest risk patient group compared with NNT of 4 among those with highest numbers of medical comorbidity. CONCLUSIONS: Monoclonal antibody treatment is associated with reduced hospitalization in vaccinated high-risk persons with mild to moderate COVID-19.

[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.

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.

Clinical efficacy and in vitro neutralization capacity of monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 delta and omicron variants.

We aimed to provide in vitro data on the neutralization capacity of different monoclonal antibody (mAb) preparations against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta and omicron variant, respectively, and describe the in vivo RNA kinetics of coronavirus disease 2019 (COVID-19) patients treated with the respective mAbs. Virus neutralization assays were performed to assess the neutralizing effect of the mAb formulations casirivimab/imdevimab and sotrovimab on the SARS-CoV-2 delta and omicron variant. Additionally, respiratory tract SARS-CoV-2 RNA kinetics are provided for 25 COVID-19 patients infected with either delta variant (n = 18) or omicron variant (n = 7) treated with the respective mAb formulations during their hospital stay. In the virus neutralization assay, sotrovimab exhibits neutralizing capacity at therapeutically achievable concentrations against the SARS-CoV-2 delta and omicron variant. In contrast, casivirimab/imdevimab had neutralizing capacity against the delta variant but failed neutralization against the omicron variant except for a very high concentration above the currently recommended therapeutic dosage. In patients with delta variant infections treated with casivirimab/imdevimab, we observed a rapid decrease of respiratory viral RNA at day 3 after mAb therapy. In contrast, no such prompt decline was observed in patients with delta variant or omicron variant infections receiving sotrovimab.

Real-world evaluation of the impact of two anti-SARS-CoV-2 monoclonal antibody regimens on COVID-19 hospitalizations in older adults.

Evidence from clinical trials suggest anti-SARS-CoV-2 monoclonal antibodies (mABs) may reduce coronavirus disease 2019 (COVID-19)-related hospitalizations. The purpose of this study was to assess the real-world impact of mAB administration on COVID-19 hospitalization among patients 65 years or older. This was a retrospective, propensity-matched cohort study that included patients aged 65 years and older who presented to the emergency department (ED) within 10 days of symptom onset of mild to moderate COVID-19 infection. Outcomes were compared between those who did and did not receive mAB therapy. The primary endpoint was the rate of hospitalization for COVID-19 within 30 days of index ED visit. A total of 137 patients receiving mABs were matched to 137 controls. Hospitalization occurred in 2.9% of mAB-treated patients compared to 14.6% of patients of the standard of care (SOC) arm (odds ratio: 0.20 [95% CI: 0.07-0.59]). There were zero intubations and zero deaths compared to 3 (2.2%) and 2 (1.5%) in the SOC group. Among the 223 patients receiving mAB in the overall cohort, adverse drug events occurred in 10 (4.5%). Treatment with mAB therapy for mild to moderate COVID-19 was associated with a substantially reduced risk of hospitalization among patients at least 65 years of age.

Successful early use of anti-SARS-CoV-2 monoclonal neutralizing antibodies in SARS-CoV-2 infected hematological patients - A Czech multicenter experience.

COVID-19 significantly impairs survival rates among hematological patients when compared to the general population. Our prospective multicentre project analyzed early administration of anti-SARS-CoV-2 spike protein neutralizing monoclonal antibodies (NmAbs) - bamlanivimab (72%) and casirivimab/imdevimab (28%) - efficacy among hematological patients with early-stage COVID-19. Mortality rate was compared to a control cohort of 575 SARS-CoV-2 positive hematological patients untreated with any specific anti-COVID-19 therapy. 88 hematological patients with lymphomas, acute leukemias, and myeloma as their most frequent underlying diagnoses (72%) were evaluated with a 97 days median follow-up after NmAb administration. One third of patients (32%) were treated with an anti-CD20 monoclonal antibody before COVID-19 diagnosis. Median time between first COVID-19 symptom and NmAb administration was 2 days. When administering NmAb, 29%, 57%, 11%, 2%, and 1% of our patients had asymptomatic, mild, moderate, severe, and critical degrees of COVID-19, respectively. 80% of baseline asymptomatic patients remained asymptomatic following NmAb administration. Median duration of COVID-19 symptoms after NmAb administration was 2.5 days. Progression to severe/critical COVID-19 occurred among a total of 17% (15/88) of our cases and numerically higher with bamlanivimab versus casirivimab/imdevimab (21% vs. 8%; p = 0.215), and myelomas (29%), lymphomas (17%) and acute leukemias (18%), respectively. During final follow-up, nine deaths (10%) were recorded - all after bamlanivimab (p = 0.056) with 8% attributed to COVID-19. Regarding "remdesivir/convalescent plasma naïve" patients, COVID-19 mortality rates were significantly lower in our NmAbs treated cohort compared to the control cohort of untreated SARS-CoV-2 positive hematological patients (6% vs. 16%, p = 0.020), respectively. Our study validated the safety and efficacy of NmAbs early use among hematological patients with newly diagnosed early-stage COVID-19 in terms of alleviating infection course and decreasing mortality. Results confirmed a more positive effect of a casirivimab/imdevimab combination versus bamlanivimab monotherapy.

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.

Treatment with anti-SARS-CoV-2 monoclonal antibodies in pregnant and postpartum women: first experiences in Florence, Italy.

PURPOSE: Pregnant and postpartum women are at increased risk of developing severe COVID-19. Monoclonal antibodies (mAbs) are now widely used in high-income countries to treat mild to moderate COVID-19 outpatients at risk for developing severe disease. Very few data are available on the use of mAbs in special populations, including pregnant and postpartum women. Here we present our early experience with mAbs in these two populations. METHODS: Electronic records of pregnant and postpartum women treated with mAbs at Careggi University Hospital, Florence, were retrieved. Relevant data were extracted (age, presence of risk factors for COVID-19, oxygen support, mAb type, gestational age, and pregnancy status). When available, outcomes at 28 days after administration were also included. RESULTS: From March 1st to September 30th 2021, eight pregnant and two postpartum women have been treated with mAbs at our center. The median age was 31 years (IQR 30-33.5, range 29-38), median gestational age was 24 weeks. Seven patients had additional risk factors. According to the Italian disposition, all patients received casirivimab/imdevimab, with five receiving a 2.4 mg dose and five receiving a 8 g dose. Eight patients improved. One developed myocarditis, considered a COVID-19 complication. Another required a transient increase of low flow oxygen support before improving and being discharged. At a 28 days follow-up, all patients were clinically recovered. We did not observe mAbs related adverse events. CONCLUSION: Although preliminary data should be interpreted with caution, it is remarkable how mAbs were well tolerated by pregnant women with COVID-19. Further data on mAbs in this special population should be collected but the use of mAbs in pregnant and postpartum patients should be considered. Even thus oral antivirals are becoming available, they are not recommended in pregnant and postpartum women. This population may specifically benefit from treatment with last generation mAbs.

High titer of antibody against the SARS-CoV-2 spike protein among patients receiving neutralizing antibody cocktail therapy with REGN-COV.

PURPOSE: Casirivimab/imdevimab (REGN-COV), a cocktail of neutralizing antibodies against the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, was shown to be an effective treatment and post-exposure prophylaxis measure for coronavirus disease 2019 (COVID-19). We assessed the antibody titers among patients who received REGN-COV with the purpose of evaluating this therapeutic and prophylactic option from the serological point of view. METHODS: We collected serological data of patients with COVID-19 who were treated with REGN-COV 1200 mg (casirivimab 600 mg/imdevimab 600 mg). Antibody titers were assessed within 24 h before and within 48 h after the administration of REGN-COV using ARCHITECT SARS-CoV-2 immunoglobulin (Ig)G (IgGNC), which is against nucleocapsid protein, and ARCHITECT SARS-CoV-2 IgG II Quant (IgGSP), which is against spike protein. RESULTS: A total of nine patients were evaluated. IgGSP was elevated after REGN-COV administration with a median of 208,370 Arbitrary Units/mL while simultaneous IgGNC remained low. With the simple linear regression model, the IgGSP after the REGN-COV administration was correlated with the reciprocal of ideal body weight. CONCLUSION: The high titer of IgGSP supports the clinical benefit of therapeutic and prophylactic use of REGN-COV from the serological point of view.

Assessment of unvaccinated and vaccinated patients with coronavirus disease 2019 (COVID-19) treated with monoclonal antibodies during the delta wave (July 1-August 20, 2021): a retrospective observational monocentric study.

BACKGROUND: Monoclonal antibodies (mAb) prevent COVID-19 progression when administered early. We compared mAb treatment outcomes among vaccinated and unvaccinated patients during Delta wave and assessed the feasibility of implementing stricter eligibility criteria in the event of mAb scarcity. METHODS: We conducted a retrospective observational study of casirivimab/imdevimab recipients with mild-to-moderate COVID-19 infection in an emergency department or outpatient infusion center (July 1-August 20, 2021). Primary outcome was all-cause hospital admission within 30 days post-treatment between vaccinated vs. unvaccinated patients during Delta surge in the Bronx, NY. RESULTS: A total of 250 patients received casirivimab/imdevimab (162 unvaccinated vs. 88 vaccinated). The median age was 39 years for unvaccinated patients, and 52 years for vaccinated patients (p < 0.0001). The median number of EUA criteria met was 1 for unvaccinated and 2 for vaccinated patients (p < 0.0001). Overall, 6% (15/250) of patients were admitted within 30 days post-treatment. Eleven unvaccinated patients (7%) were admitted within 30-days compared to 4 (5%) vaccinated patients (p = 0.48). CONCLUSIONS: All-cause 30-day admission was not statistically different between vaccinated and unvaccinated patients. When federal allocation of therapies is limited, programs must prioritize patients at highest risk of hospitalization and death regardless of vaccination status.

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.

Breakthrough COVID-19 after SARS-CoV-2 vaccination in solid organ transplant recipients: An analysis of symptomatic cases and monoclonal antibody therapy.

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risk for complications from SARS-CoV-2 infection. Little is known regarding clinical course and outcomes of breakthrough COVID-19 in the fully vaccinated SOT population. We sought to describe our cohort of SOT recipients who developed symptomatic breakthrough COVID-19 after full vaccination. METHODS: We conducted a retrospective review of SOT recipients diagnosed with COVID-19 at least 14 days after completing SARS-CoV-2 vaccination. Patients were analyzed according to those presenting with mild-to-moderate and severe COVID-19, respectively. We described presenting characteristics, COVID-19 therapy, and analyzed outcomes including emergency department (ED) visits, hospitalization, and intensive care unit (ICU) admission. RESULTS: Thirty-five patients met inclusion criteria. These had a mean age of 60.8 years and kidney transplant was the most common SOT type. Five patients presented with severe COVID-19 at diagnosis, all requiring hospitalization without ICU admission. From the 30 patients who presented with mild-to-moderate infection, 28 received casirivimab-imdevimab. Four of these 28 (14.3%) had an ED visit, with one requiring hospital admission (3.4%). No patients required ICU admission. CONCLUSION: Breakthrough COVID-19 may occur in SOT recipients after full vaccination, though they appear to have acceptable outcomes. Anti-spike monoclonal antibody therapy for eligible SOT patients may have mitigated clinical progression and improved the outcomes. Further study with large cohorts is warranted.

Monoclonal antibody treatment for COVID-19 in solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at high risk for severe coronavirus disease 2019 (COVID-19). Studies suggest that early intervention with monoclonal antibody (MAB) treatment directed against the SARS-CoV-2 spike protein may reduce the risk of emergency department visits or hospitalization for COVID-19, especially in high-risk patients. Herein, we describe our single-center experience of 93 SOT (50 kidney, 17 liver, 11 lung, nine heart, and six dual-organ) recipients with mild to moderate COVID-19 who were treated with bamlanivimab or casirivimab-imdevimab per emergency use authorization guidelines. Median age of recipients was 55 [(Interquartile range) 44-63] years, and 41% were diabetic. Median time from transplant to MAB was 64 (IQR 24-122) months and median time from the onset of COVID-19 symptoms to the infusion was 6 (IQR 4-7) days. All patients had a minimum 30 days of study follow-up. The 30-day hospitalization rate for COVID-19-directed therapy was 8.7%. Infusion-related adverse events were rare and generally mild. Biopsy-proven organ rejection occurred in two patients, and there were no graft losses or deaths. A comparator group of 72 SOT recipients diagnosed with COVID-19 who were eligible but did not receive MAB treatment had a higher 30-day hospitalization rate for COVID-19-directed therapy (15.3%), although this difference was not statistically significant, after adjustment for age (Odds Ratio 0.49 [95% Confidence Interval 0.18-1.32], p = 0.16). Our experience suggests that MAB treatment, with respect to the available MAB formulations and circulating viral variants present during our study period, may provide favorable outcomes for mild to moderate COVID-19 in SOT recipients.

Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic.

Background: Mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. Methods: We enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). Results: The casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature (≥ 38°C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). Conclusion: This real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge.

REGN-COV2 antibody cocktail in patients with SARS-CoV-2: Observational study from a single institution in Japan.

INTRODUCTION: A new treatment for coronavirus disease (COVID-19), REGN-COV2, a cocktail consisting of two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been approved for patients at a risk of developing more severe disease. METHODS: We retrospectively reviewed patients recently diagnosed with COVID-19 with risk factors for severe infection, who were treated with the REGN-COV2 antibody cocktail between July and September 2021. The REGN-COV2 antibody cocktail was administered to patients within 7 days of disease onset, with an oxygen saturation of >93%, and with at least one comorbidity. We investigated the percentage of patients with COVID-19-related hospitalization or death, the duration of symptoms after treatment, and the adverse effects of treatment. RESULTS: A total of 108 patients were reviewed. Of them, 64% were aged ≥50 years, 31% had obesity, 36% had hypertension, and 18% had diabetes. In addition, 49% had multiple risk factors for severe COVID-19. Overall, 12 patients (11%) needed COVID-19-related hospitalization. No adverse effects of treatment were observed. CONCLUSIONS: This study shows that treatment with the REGN-COV2 antibody cocktail is safe and beneficial in patients at a risk of developing severe COVID-19.