AbstractIn late 2019, SARS-Cov-2 – a novel coronavirus emerged,which shocked the world. COVID-19 is a disease that devel-ops in the setting of SARS-Cov-2 infection and is character-ized by high mortality and complications both in its acuteand long-term course. By 2020, WHO announced covid-19as a pandemic. Individuals with comorbidities are at risk ofbeing severely infected and may have poor prognosis.Based on statistical data more than 40% of patients in-fected with COVID-19 have different comorbidities: Obesity,diabetes, malignancy, COPD, liver and renal diseases, car-diovascular diseases, hypertension being most prevalent.Up to 75% of fatal cases were having comorbidities. Diseas-es like hypertension, diabetes and respiratory pathologieswere most associated with fatal outcomes.It is known that interaction between SARS-Cov2 spikeprotein and ACE-2 receptor underlies virus entry into thecells. Since this receptor is expressed by various cells, in-cluding pulmonary, cardiac, renal, intestinal, endothelial,neuro-glial tissue, the infection is characterized by multior-gan involvement. In addition to that, when the virus acti-vates macrophages great amount of cytokines (IL-1, IL-6,and TNFá) and chemokines (CXCL10 and CCL2) are liberat-ed into the bloodstream causing cytokine storm, the mas-sive immune response often leading to multiorgan failure.These pathologic processes are especially evident in co-morbid patients.According to WHO Guideline 2022 Janus kinase inhibi-tor Baricitinib is strongly recommended for patients withsevere or critical COVID-19, while there’s a conditional rec-ommendation against ruxolitinib or Tofacitinib. WHO givesa conditional recommendation for Sotrovimab for patientswith non-severe COVID-19, it’s important to emphasize thatthere’s a strong recommendation against the use of conva-lescent plasma in these patients. In patients with severe orcritical COVID-19 convalescent plasma should not be usedexcept for research purposes. IL-6 Blockers (tocilizumab orsarilumab) are strongly recommended for patients with se-vere or critical COVID-19. Ivermectin should not be usedexcept in the context of a clinical trial, regardless of diseaseseverity. There’s a strong recommendation against the useof Hydroxychloroquine and Lopinavir/ritonavir regardlessof disease severity. Remdisivir is suggested not to be usedin patients with COVID-19, regardless of disease severity.Treatment with systemic corticosteroids is strongly recom-mended for severe or critical COVID-19, while there’s a con-ditional recommendation against their use in patients withnon-severe COVID-19.Massive immunological dysregulation and tissue hypoxiaunderlie the pathogenesis of SARS-Cov2 infection. Variouscomorbidities enhance those effects of the infection and alsoenable virus spread and persistence in the human body. SinceCovid-19 comorbidities seem to be important determinantsof disease severity, proper management should be used inhigh-risk patients.
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