Th17-connected cytokines have also been associated with further release of proinflammatory cytokines and ARDS [15]. Immunomodulating drugs that can limit the hyperinflammatory pathogenic cellular and humoral immune response caused by SARS-CoV-2 infection are being investigated and implemented into the clinical management of patients with COVID-19. COVID-19. We also describe data surrounding COVID-19 vaccination of the SOT recipient. Understanding the extent and limitations of observational and clinical trial data for the prevention and treatment of COVID-19 specific to the SOT population is crucial for optimal management. Although minimal data exist on clinical outcomes among SOT recipients treated with varying COVID-19 therapeutics, reviewing these agents and the studies that have led to their inclusion or exclusion in clinical management of COVID-19 highlights the need for further studies of these therapeutics in SOT patients with COVID-19. Keywords: solid organ transplant, COVID-19, vaccine, SARS-CoV-2, immunosuppressed 1. Introduction Management and prevention of Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can be challenging among solid organ transplant (SOT) recipients. Frequent healthcare visits, the presence of medical comorbidities, and modulated host immune response due to immunosuppressive medication place SOT recipients at high risk of contracting SARS-CoV-2 infection and developing severe COVID-19. Mortality rates reported among SOT recipients with COVID-19 vary widely from 3% to over 30% depending on organ type, comorbid conditions, geographical location, COVID-19 treatment, and time of report during the pandemic [1,2]. Data are conflicting as to whether SOT recipients have higher risk of mortality compared with non-SOT recipients [2,3,4,5,6,7,8]. Furthermore, SOT recipients often have comorbidities, such as diabetes, chronic kidney disease, and cardiac disease, that have been associated with more severe cases of COVID-19 and an Anagliptin increased risk of mortality. As such, it is difficult to determine the attributable impact of SOT recipient status on COVID-19 morbidity and mortality. During the COVID-19 pandemic, scientific efforts have advanced therapeutic options and vaccine development. In some cases, these therapeutics have halted the progression of COVID-19 or have improved survival. In this review, we summarize the data surrounding treatment options for COVID-19, with a focus on data specific to SOT recipients, including literature on vaccination against COVID-19 in SOT recipients. Throughout this review, severity of illness categories are defined in accordance with National Institutes of Health (NIH) COVID-19 Treatment Guidelines [9]. Mild illness is defined as signs and symptoms of COVID-19 without an oxygen saturation (SpO2) <94% on room air, dyspnea or abnormal chest imaging, moderate illness is defined as evidence of lower respiratory disease clinically or on imaging with an SpO2 94% on room air, severe illness is defined as an SpO2 <94% on room air, and critical illness is defined as respiratory failure, septic shock, or multiple organ dysfunction. 2. Basic Principles 2.1. Virology Fundamental concepts of both SARS-CoV-2 virology and host immune response during infection illuminate therapeutic targets for antiviral Rabbit Polyclonal to AL2S7 and immunomodulating drugs. Viral transmission of SARS-CoV-2, an enveloped, Anagliptin positive-sense, single-stranded ribonucleic acid (RNA) betacoronavirus, primarily occurs through inhalation of infected respiratory droplets, leading to an interface of SARS-CoV-2 with human respiratory tract and alveolar epithelial cells, vascular endothelial cells, and alveolar macrophages [10]. SARS-CoV-2 spike glycoprotein (S protein) then binds to the ACE2 receptor of target host cells in synergy with the host transmembrane serine protease 2, allowing membrane fusion and release of the viral genome into host cytoplasm through an endocytic pathway [11]. Following host cell entry, the virus is disassembled to release nucleocapsid and viral genome, which host ribosomes translate into polyproteins [11]. Proteases cleave polyproteins into structural and non-structural proteins that include the replication-transcription complex, containing the RNA-dependent RNA polymerase that is highly conserved and critical to the SARS-CoV-2 life cycle by mediating transcription and replication of the RNA genome [11]. The process concludes with assembly of Anagliptin virion components into the endoplasmic reticulum Golgi intermediate compartment complex, virus maturation, and release from infected Anagliptin cells by exocytosis [11]. This leads to infection of neighboring cells and viremia. Importantly, inhibitors of messenger RNA (mRNA) translation have demonstrated in vitro antiviral activity [12]. 2.2. Immunology Morbidity and mortality associated with COVID-19 often relate to an inflammatory phase following infection, respiratory failure from acute respiratory distress syndrome (ARDS), and a cytokine storm-like syndrome. Once SARS-CoV-2 enters its host cells, active replication and release of the virus causes a highly inflammatory programmed cell death [13]. Unlike many other respiratory viral infections, interferon (IFN)-1 and IFN-III response is reduced in COVID-19, dampening early host innate antiviral activity [14]. Pathogen-associated molecular patterns and damage-associated molecular patterns are released and recognized by neighboring alveolar epithelial cell and alveolar macrophage pattern-recognition receptors [13]. This process activates down-stream proinflammatory transcription factors, leading to production of chemokines and cytokines that recruit monocytes, NK cells, dendritic cells, and lymphocytes [13,14]. A protective immune response involves early rapid clearance of infected cells, functional CD4 T cell.