Objectives In March 2020, the World Health Organization declared that an infectious respiratory disease caused by a new severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, causing coronavirus disease 2019 (COVID-19)] became a pandemic. In our study, we have analyzed a large publicly available dataset, the Genome Aggregation Database (gnomAD), as well as a cohort of 37 Russian patients with COVID-19 to assess the influence of different classes of genetic variants in the angiotensin-converting enzyme-2 ( ACE2 ) gene on the susceptibility to COVID-19 and the severity of disease outcome. Results We demonstrate that the European populations slightly differ in alternative allele frequencies at the 2,754 variant sites in ACE2 identified in the gnomAD database. We find that the Southern European population has a lower frequency of missense variants and slightly higher frequency of regulatory variants. However, we found no statistical support for the significance of these differences. We also show that the Russian population is similar to other European populations when comparing the frequencies of the ACE2 variants. Evaluation of the effect of various classes of ACE2 variants on COVID-19 outcome in a cohort of Russian patients showed that common missense and regulatory variants do not explain the differences in disease severity. At the same time, we find several rare ACE2 variants (including rs146598386, rs73195521, rs755766792, and others) that are likely to affect the outcome of COVID-19. Our results demonstrate that the spectrum of genetic variants in ACE2 may partially explain the differences in severity of the COVID-19 outcome.

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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.