Monoclonal Antibody Therapy For High-Risk Coronavirus (COVID 19) Patients With Mild To Moderate Disease Presentations

Since being declared a global pandemic by the World Health Organization WHO), Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating effect on the global health and economy. The virus primarily affects the respiratory system and is spread from person to person via respiratory particles from coughing and sneezing. The majority of transmission occurs from close contact with presymptomatic, asymptomatic, or symptomatic carriers. The early course of the pandemic was characterized by the rapid spread of the virus that created an urgency to mitigate this new viral illness with experimental therapies and drug repurposing. Since then, due to an intense global research effort, significant progress has been made that has resulted in the development of novel therapeutics and vaccines at an unprecedented speed, leading to favorable patient outcomes. Currently, a variety of therapeutic options that include antiviral medications, monoclonal antibodies, and immunomodulatory agents are available in the management of COVID-19. However, the therapeutic potential and clinical use of these drugs are limited and specifically based on the stage of the illness. The pathogenesis of COVID-19 illness occurs in two distinct phases, an early stage characterized by profound SARS-CoV-2 viral replication followed by a late phase characterized by a hyperinflammatory state induced by the release of cytokines such as tumor necrosis factor-α(TNF α), granulocyte-macrophage colony-stimulating factor (GM-CSF), Interleukin-(IL-1), IL-6, interferon (IFN)-γ and activation of the coagulation system resulting in a prothrombotic state. Antiviral therapy and antibody-based treatments are likely to be more effective if used during the early phase of the illness, and immunomodulating therapies either alone or in combination with antiviral and antibody-based therapies may be more effective when used in the later stage to combat the cytokine-mediated hyperinflammatory state that causes severe illness.Individuals of all ages are at risk for infection and severe disease. However, individuals aged ≥60 years and with underlying medical comorbidities (obesity, cardiovascular disease, chronic kidney disease, diabetes, chronic lung disease, smoking, cancer, solid organ or hematopoietic stem cell transplant recipients) are at increased risk of developing severe COVID-19 infection. The percentage of COVID-19 patients requiring hospitalization was six times higher in those with preexisting medical conditions than those without medical conditions (45.4% vs. 7.6%) based on an analysis by Stokes et al. of confirmed cases reported to the CDC during January 22–May 30, 2020.A promising approach to address the COVID-19 associated mortality and prevent the increased utilization of healthcare resources is by terminating the progression of viral replication, thereby preventing the progression to the hyperinflammatory stage of COVID-19, which causes severe illness in high-risk nonhospitalized patients. Initially, the focus of treatment was directed mainly towards hospitalized patients with COVID-19 illness. However, the clinical focus over the course of the pandemic has expanded toward combatting the illness early on by reducing the viral load in patients with early disease, thus attempting to halt the disease progression.Monoclonal antibodies targeting the spike protein of the SARS-CoV-2 have yielded positive in vitro results. They are considered a promising approach in managing nonhospitalized patients with mild to moderate COVID-19 who are at high risk of developing severe illness. This review discusses the mechanism of action of monoclonal antibodies against SARS-CoV-2 and current clinical indications of monoclonal antibody therapy for nonhospitalized patients with mild to moderate COVID-19 illness who are at high risk of developing severe illness. Monoclonal Antibodies in COVID-19 Monoclonal antibodies (mAbs) are immune system proteins developed from a single cell lineage that demonstrate a high affinity for their target cell. Monoclonal antibodies were first developed by Kohler and Milstein in 1975 using hybridoma technology. Since then, significant progress has been made in the molecular engineering world that has enabled the establishment of monoclonal antibodies as targeted therapies in various neoplastic conditions, autoimmune, post-transplant immunosuppression, and infectious diseases.When used as antiviral therapies, neutralizing antibodies play an indispensable part in achieving passive antiviral immunity and are also instrumental in the prevention or regulation of many viral illnesses. Over the years, passive immunization against many viral diseases was achieved by administering polyclonal sera obtained from convalescent human donors or animals. However, polyclonal antibody preparations are increasingly being replaced by monoclonal antibodies by virtue of them, demonstrating a favorable safety profile and target specificity when used in different viral diseases. Palivizumab was the first antiviral monoclonal antibody approved by the US Food and Drug Administration (FDA) for prophylaxis of RSV in high-risk infants. Over the years, significant developments in antibody engineering, improved understanding of the biology of viruses, and the direct and indirect effect of monoclonal antibodies on viral infections has resulted in the development of many novel monoclonal antibodies. Like other antiviral drugs, monoclonal antibodies, when used as antiviral agents, are also susceptible to developing resistance as a result of alterations in the viral genome which can alter the pathogenic potential of the virus resulting in the emergence of viral escape mutants, which may render the virus-resistant to a specific monoclonal antibody. To counter this viral escape phenomenon, a combination of monoclonal antibodies, commonly referred to as antibody cocktails, have been proposed with the rationale that combining two specific monoclonal antibodies that complement each other can preventing neutralization escape by targeting multiple viral epitopes. There are an estimated 70 monoclonal antibodies currently in development or clinical trials to treat COVID-19. The FDA has granted four EUA for clinical use as combination antibody cocktails.