Outcomes of Bebtelovimab Therapy in Patients With Solid Organ Transplantation With Mild and Moderate COVID-19.

Solid organ transplant recipients (SOTRs) are at greater risk of poorer outcomes from coronavirus disease 2019 (COVID-19) as compared to the general population. Because of significant drug-drug interactions between nirmatrelvir-ritonavir and immunosuppressive agents as well as logistical challenges of outpatient administration of remdesivir, anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) monoclonal antibodies (mAbs) had been the mainstay of outpatient treatment of COVID-19 among SOTRs, with bamlanivimab, casirivimab-imdevimab, and sotrovimab having been previously granted emergency use authorization by the Food and Drug Administration (FDA). The challenge with the ongoing use of these monoclonal antibodies is the loss of efficacy against emerging variants of SARS-CoV-2. Bebtelovimab, which retained efficacy against early subvariants of Omicron, was granted emergency use authorization by the Food and Drug Administration when Omicron BA.4 and BA.5 became the predominant variants in the United States. However, the study based on which bebtelovimab was authorized by the FDA did not include SOTRs. The only available safety and efficacy data on these patients are from retrospective studies. In our retrospective analysis of 62 SOTRs who received bebtelovimab infusion between May 11, 2022, and October 11, 2022, 28 had a kidney transplant, 18 had a liver transplant, 10 had a heart transplant, and six had multi-organ transplants (liver/kidney: 4, heart/kidney: 2). None of the patients reported infusion-associated adverse reaction. Only one (1.6%) patient developed progression of COVID-19, requiring subsequent treatment with remdesivir, steroids, and oxygen supplementation. The rate of need for intensive care and death from COVID-19 during the 30-day follow-up period was 0%.

Early Treatment with Monoclonal Antibodies or Convalescent Plasma Reduces Mortality in Non-Vaccinated COVID-19 High-Risk Patients.

Vulnerable patients such as immunosuppressed or elderly patients are at high risk for a severe course of COVID-19 upon SARS-CoV-2 infection. Immunotherapy with SARS-CoV-2 specific monoclonal antibodies (mAb) or convalescent plasma represents a considerable treatment option to protect these patients from a severe or lethal course of infection. However, monoclonal antibodies are not always available or less effective against emerging SARS-CoV-2 variants. Convalescent plasma is more commonly available and may represent a good treatment alternative in low-income countries. We retrospectively evaluated outcomes in individuals treated with mAbs or convalescent plasma and compared the 30-day overall survival with a patient cohort that received supportive care due to a lack of SARS-CoV-2 specific therapies between March 2020 and April 2021. Our data demonstrate that mAb treatment is highly effective in preventing severe courses of SARS-CoV-2 infection. All patients treated with mAb survived. Treatment with convalescent plasma improved overall survival to 82% compared with 61% in patients without SARS-CoV-2 targeted therapy. Our data indicate that early convalescent plasma treatment may be an option to improve the overall survival of high-risk COVID-19 patients. This is especially true when other antiviral drugs are not available or their efficacy is significantly reduced, which may be the case with emerging SARS-CoV-2 variants.

Effectiveness of Sotrovimab in the Omicron Storm Time: A Case Series.

Neutralizing monoclonal antibodies (mAbs) for pre- and post-exposure prophylaxis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are largely used to prevent the progression of the disease by blocking viral attachment, host cell entry, and infectivity. Sotrovimab, like other available mAbs, has been developed against the receptor binding Domain of the Spike (S) glycoprotein of the virus. Nevertheless, the latest Omicron variant has shown marked mutations within the S gene, thus opening the question of the efficacy of these neutralizing molecules towards this novel variant. In the present observational study, we describe the effects of Sotrovimab in the treatment of 15 fully vaccinated patients, infected by SARS-CoV-2 Omicron sub-variants, who were selected on the basis of factors widely considered to affect a worse prognosis: immune suppression (n = 12) and/or chronic kidney disease (n = 5) with evidence of interstitial pneumonia in nine patients. The effectiveness of Sotrovimab in the treatment of severe cases of COVID-19 was demonstrated by the regression of symptoms (mean 5.7 days), no need of hospitalisation, improvement of general health conditions and viral clearance within 30 days in all patients. In conclusion, although loss or reduction of mAbs neutralizing activity against the Omicron variant have been described, Sotrovimab has clinically proven to be a safe and useful treatment for patients with high risk of progression to severe COVID-19 infected by Omicron sub-variants.

Use of Casirivimab and Imdevimab for the Treatment of COVID-19.

The authors present three cases of unvaccinated coronavirus disease 2019 (COVID-19) patients who exhibited symptoms of fever, sore throat, nausea, diarrhea, congestion, and headache. Although they refused COVID-19 vaccination, they presented for the casirivimab and imdevimab monoclonal antibody cocktail, which resulted in the resolution of all symptoms. The authors describe the mechanisms and importance of monoclonal antibody treatment for high-risk and unvaccinated patients infected with SARS-CoV-2.

How does SARS-CoV-2 infection impact on immunity, procession and treatment of pan cancers.

We identified 14 immune-related differentially Expressed Genes (DEGs) between COVID-19 patients and normal controls and the receiver operator characteristic curve results showed that they could be used to discriminate COVID-19 patients from healthy controls. Single-sample gene set enrichment analysis and CIBERSORT analysis displayed immune landscape of COVID-19 patients that the fraction of immune cells (like B cell subtypes and T cell subtypes) decreased distinctly in the first SARS-CoV-2 infection which may further weaken immunity of cancer patients and increasing inflammatory cells (Neutrophils and Macrophages) may further promote inflammatory response of cancer patients. Based on expression levels of 14 DEGs we found that first SARS-CoV-2 infection may accelerate progression of cancer patients by Kaplan-Meier survival, immune subtypes and tumor microenvironment analyses, and may weaken anti-PD-1 monoclonal antibody treatment effect of cancer patients by weighted gene co-expression network, tumor mutation burden and microsatellite instability analysis. The second SARS-CoV-2 infection was beneficial to control development of tumor seemingly, but it may be difficult for cancer patients to experience destroy successfully from first SARS-CoV-2 infection, let alone benefits from second SARS-CoV-2 infection. In addition, this study also emphasized significance of multi-factor analysis when analyzing impacts of SARS-CoV-2 infection on cancer patients.

Long-term cellular immune response in immunocompromised unvaccinated COVID-19 patients undergoing monoclonal antibody treatment.

Immunocompromised patients are at increased risk for a severe course of COVID-19. Treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with anti-SARS-CoV-2 monoclonal antibodies (mAbs) has become widely accepted. However, the effects of mAb treatment on the long-term primary cellular response to SARS-CoV-2 are unknown. In the following study, we investigated the long-term cellular immune responses to SARS-CoV-2 Spike S1, Membrane (M) and Nucleocapsid (N) antigens using the ELISpot assay in unvaccinated, mAb-treated immunocompromised high-risk patients. Anti-SARS-CoV-2 mAb untreated though vaccinated COVID-19 immunocompromised patients, vaccinated SARS-CoV-2 immunocompromised patients without COVID-19 and vaccinated healthy control subjects served as control groups. The cellular immune response was determined at a median of 5 months after SARS-CoV-2 infection. Our data suggest that immunocompromised patients develop an endogenous long-term cellular immune response after COVID-19, although at low levels. A better understanding of the cellular immune response will help guide clinical decision making for these vulnerable patient cohorts.

Newly Emerged Antiviral Strategies for SARS-CoV-2: From Deciphering Viral Protein Structural Function to the Development of Vaccines, Antibodies, and Small Molecules.

Coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most severe health crisis, causing extraordinary economic disruption worldwide. SARS-CoV-2 is a single-stranded RNA-enveloped virus. The process of viral replication and particle packaging is finished in host cells. Viral proteins, including both structural and nonstructural proteins, play important roles in the viral life cycle, which also provides the targets of treatment. Therefore, a better understanding of the structural function of virus proteins is crucial to speed up the development of vaccines and therapeutic strategies. Currently, the structure and function of proteins encoded by the SARS-CoV-2 genome are reviewed by several studies. However, most of them are based on the analysis of SARS-CoV-1 particles, lacking a systematic review update for SARS-CoV-2. Here, we specifically focus on the structure and function of proteins encoded by SARS-CoV-2. Viral proteins that contribute to COVID-19 infection and disease pathogenesis are reviewed according to the most recent research findings. The structure-function correlation of viral proteins provides a fundamental rationale for vaccine development and targeted therapy. Then, current antiviral vaccines are updated, such as inactive viral vaccines and protein-based vaccines and DNA, mRNA, and circular RNA vaccines. A summary of other therapeutic options is also reviewed, including monoclonal antibodies such as a cross-neutralizer antibody, a constructed cobinding antibody, a dual functional monoclonal antibody, an antibody cocktail, and an engineered bispecific antibody, as well as peptide-based inhibitors, chemical compounds, and clustered regularly interspaced short palindromic repeats (CRISPR) exploration. Overall, viral proteins and their functions provide the basis for targeted therapy and vaccine development.

Vaginal delivery after improvement in COVID-19 by monoclonal antibody treatment: A case report and literature review.

As the COVID-19 pandemic persists, pregnant women have been increasingly affected worldwide. Women during the last trimester of pregnancy are susceptible to severe COVID-19, and there are many challenges towards its treatment. Monoclonal antibody treatment (MAT) is approved for COVID-19 patients to reduce disease severity. However, there are few reports on the MAT in perinatal women. Herein, we report a 39-year-old pregnant female (36 weeks and 6 days of gestation) with improvement in COVID-19 pneumonia after treatment with casiribimab/imdevimab, resulting in successful vaginal delivery (a 2.868 kg male newborn), along with a literature review. Early diagnosis and treatment of pregnant women with COVID-19 are important. Infectious diseases doctors and/or obstetricians should be aware of the MAT option administered to perinatal COVID-19 women to reduce disease severity.

A pyrosequencing protocol for rapid identification of SARS-CoV-2 variants.

Next-generation sequencing (NGS) is the primary method used to monitor the distribution and emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants around the world; however, it is costly and time-consuming to perform and is not widely available in low-resourced geographical regions. Pyrosequencing has the potential to augment surveillance efforts by providing information on specific targeted mutations for rapid identification of circulating and emerging variants. The current study describes the development of a reverse transcription (RT)-PCR-pyrosequencing assay targeting >65 spike protein gene (S) mutations of SARS-CoV-2, which permits differentiation of commonly reported variants currently circulating in the United States with a high degree of confidence. Variants typed using the assay included B.1.1.7 (Alpha), B.1.1.529 (Omicron), B.1.351 (Beta), B.1.375, B.1.427/429 (Epsilon), B.1.525 (Eta), B.1.526.1 (Iota), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.621 (Mu), P1 (Gamma), and B.1.1 variants, all of which were confirmed by the NGS data. An electronic typing tool was developed to aid in the identification of variants based on mutations detected by pyrosequencing. The assay could provide an important typing tool for rapid identification of candidate patients for monoclonal antibody therapies and a method to supplement SARS-CoV-2 surveillance efforts by identification of circulating variants and novel emerging lineages.

Effects of Casirivimab/Imdevimab Monoclonal Antibody Treatment among Vaccinated Patients Infected by SARS-CoV-2 Delta Variant.

There is a growing interest in using monoclonal antibodies (mAbs) in the early stages of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection to prevent disease progression. Little is known about the efficacy of mAbs against the delta variant of concern and its clinical presentations. We evaluated the effect of casirivimab/imdevimab treatment among five delta vaccine breakthrough patients. Symptomatic non-hospitalized vaccinated patients were submitted to nasopharyngeal swabs for the detection of SARS-CoV-2 and Next-Generation Sequencing (NGS). Blood analysis and chest Computed Tomography were also performed. A cocktail of casirivimab/imdevimab was administrated, and patients were monitored weekly. Clinical evolution was evaluated by the regression of the symptoms, negative results by real-time RT-PCR, and by the need of hospitalization: these aspects were considered as significant outcomes. In four cases, symptom reversion and viral load reduction were observed within 2 days and 7 days after mAbs treatment, respectively. Only one case, suffering from thymoma, was hospitalized 2 days later because of respiratory failure, which reverted within 18 days. mAbs treatment seems to be safe and effective against the delta variant and its clinical manifestations.

Staffing and Capacity Planning for SARS-CoV-2 Monoclonal Antibody Infusion Facilities: A Performance Estimation Calculator Based on Discrete-Event Simulations.

Background: The COVID-19 pandemic has significantly stressed healthcare systems. The addition of monoclonal antibody (mAb) infusions, which prevent severe disease and reduce hospitalizations, to the repertoire of COVID-19 countermeasures offers the opportunity to reduce system stress but requires strategic planning and use of novel approaches. Our objective was to develop a web-based decision-support tool to help existing and future mAb infusion facilities make better and more informed staffing and capacity decisions. Materials and Methods: Using real-world observations from three medical centers operating with federal field team support, we developed a discrete-event simulation model and performed simulation experiments to assess performance of mAb infusion sites under different conditions. Results: 162,000 scenarios were evaluated by simulations. Our analyses revealed that it was more effective to add check-in staff than to add additional nurses for middle-to-large size sites with ≥2 infusion nurses; that scheduled appointments performed better than walk-ins when patient load was not high; and that reducing infusion time was particularly impactful when load on resources was only slightly above manageable levels. Discussion: Physical capacity, check-in staff, and infusion time were as important as nurses for mAb sites. Health systems can effectively operate an infusion center under different conditions to provide mAb therapeutics even with relatively low investments in physical resources and staff. Conclusion: Simulations of mAb infusion sites were used to create a capacity planning tool to optimize resource utility and allocation in constrained pandemic conditions, and more efficiently treat COVID-19 patients at existing and future mAb infusion sites.

Use of a Unique Mobile Medical Asset in COVID Monoclonal Antibody Treatment.

The COVID-19 pandemic and the subsequent surge of patients presented to emergency departments has forever changed the paradigm of delivering emergency care. The highly infectious nature of the 2019 Novel Coronavirus, or COVID-19, mandated strict environmental changes, novel patient care, and flexible strategies to continue to deliver efficient emergency care while maintaining appropriate physical distancing between suspect and non-suspect COVID-19 patients. The engagement of a unique rapidly deployable Mobile Satellite Emergency Department (MSED) with scalable capability from prompt care to resuscitation level allowed the emergency care team to optimize patient care and throughput. The MSED was strategically located adjacent to the ambulance entrance. While initially deployed to increase Emergency Department surge capacity, the MSED was repurposed to cohort and treat COVID patients with the monoclonal antibody, Bamlanivimab, who were expected to be discharged after treatment. This allowed for more efficient use of Emergency Department resources, including physical space and staffing.

Development of Coronavirus Treatments Using Neutralizing Antibodies.

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, was first reported in December 2019 in Wuhan, Hubei province, China. This virus has led to 61.8 million cases worldwide being reported as of December 1st, 2020. Currently, there are no definite approved therapies endorsed by the World Health Organization for COVID-19, focusing only on supportive care. Treatment centers around symptom management, including oxygen therapy or invasive mechanical ventilation. Immunotherapy has the potential to play a role in the treatment of SARS-CoV-2. Monoclonal antibodies (mAbs), in particular, is a relatively new approach in the world of infectious diseases and has the benefit of overcoming challenges with serum therapy and intravenous immunoglobulins preparations. Here, we reviewed the articles published in PubMed with the purpose of summarizing the currently available evidence for the use of neutralizing antibodies as a potential treatment for coronaviruses. Studies reporting in vivo results were summarized and analyzed. Despite promising data from some studies, none of them progressed to clinical trials. It is expected that neutralizing antibodies might offer an alternative for COVID-19 treatment. Thus, there is a need for randomized trials to understand the potential use of this treatment.