No abstract

Since its first detection, coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has spread rapidly around the world. Although coronavirus SARS-CoV-2 primarily targets the respiratory system, complications in other organ systems (cardiovascular, neurological, and renal) can also contribute to death from the disease. Clinical experience thus far has shown substantial heterogeneity in the trajectory of SARS-CoV-2 infection, spanning from asymptomatic to mild, moderate, and severe disease forms with low survival rates. Accurate prediction of COVID-19 mortality and the identification of contributing factors would allow for targeted strategies in patients with the high risk of death. We aimed to identify clinical and laboratory features that contributed the most to this prediction. An improved understanding of predictive factors for COVID-19 is crucial for identify those with higher risk of mortality and for clinical decision making to reduce the risk of death. The main risk factors for the severe course of COVID-19, the development of complications and death include old age, concomitant diseases (cardiovascular diseases, chronic lung diseases, diabetes mellitus and hypertension), body temperature 37.8C, oxygen saturation 92%, quantitative and functional depletion of innate immunity, bilateral pulmonary infiltrates, increased levels of laboratory parameters of systemic inflammation, respiratory, cardiac, renal and/or hepatic failure. Proper assessment of prognostic factors and careful monitoring to ensure the necessary interventions at the appropriate time in high-risk patients can reduce the fatality rate from COVID-19.

Since SARS-CoV-2 first appeared in humans, the scientific community has tried to gather as much information as possible in order to find effective strategies for the containment and treatment this pandemic coronavirus. We reviewed the current published literature on SARS-CoV-2 with an emphasis on the distribution of SARS-CoV-2 in tissues and body fluids, as well as data on the expression of its input receptors on the cell surface. COVID-19 affects many organ systems in many ways. These varied manifestations are associated with viral tropism and immune responses of the infected person, but the exact mechanisms are not yet fully understood. We emphasize the broad organotropism of SARS-CoV-2, as many studies have identified viral components (RNA, proteins) in many organs, including immune cells, pharynx, trachea, lungs, blood, heart, blood vessels, intestines, brain, kidneys, and male reproductive organs. Viral components are present in various body fluids, such as mucus, saliva, urine, cerebrospinal fluid, semen and breast milk. The main SARS-CoV-2 receptor, ACE2, is expressed at different levels in many tissues throughout the human body, but its expression levels do not always correspond to the detection of SARS-CoV-2, indicating a complex interaction between the virus and humans. We also highlight the role of the renin-angiotensin aldosterone system and its inhibitors in the context of COVID-19. In addition, SARS-CoV-2 has various strategies that are widely used in various tissues to evade innate antiviral immunity. Targeting immune evasion mediators of the virus can block its replication in COVID-19 patients. Together, these data shed light on the current understanding of the pathogenesis of SARS-CoV-2 and lay the groundwork for better diagnosis and treatment of patients with COVID-19.

COVID-19 is characterized by a wide range of clinical manifestations, from asymptomatic to extremely severe. At the onset of the pandemic, it became clear that old age and chronic illness were the major risk factors. However, they do not fully explain the variety of symptoms and complications of the SARS-COV-2 coronavirus infection. The research on genetic risk factors for COVID-19 is still at its early stages. A number of mutations and polymorphisms have been identified that affect the structure and stability of proteins factors of susceptibility to SARS-COV-2 infection, as well as a predisposition to the development of respiratory failure and the need for intensive care. Most of the identified genetic factors are related to the function of the immune system. On the other hand, the genetic polymorphism of the virus itself affects the COVID-19 spread and severity of its course . The genome of the virus accumulates mutations and evolves towards increasing contagiousness, replicative ability and evasion from the host's immune system. Genetic determinants of the COVID-19 infection are potential therapeutic targets. Studying them will provide information for the development of drugs and vaccines to combat the pandemic.

Precision (target) medicine is proposed as a new strategy to identify and develop new highly selective drugs against specific targets for the disease and more precise tailoring of medicines to the target populations of patients. Precision medicine can be an important approach to create more novel and safer therapeutics (tyrosine kinase inhibitors, tumour specific monoclonal antibodies) for patients with gene mutation, aberrations, or protein over-expression. Precision medicine requires an understanding mutational processes, and heterogeneity between cancer cells during tumor evolution. The present review briefly define various heterogeneities and potential associations with drug efficacy and resistance, emphasize the importance to develop functional biomarkers to monitor drug efficacy and resistance, and define opportunities and challenges of precision medicine for clinical practice.