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In a study of 548 patients with severe disease treated with high-dose corticosteroids, patients had an increased death rate than those not treated with corticosteroids (93). Some trials are exploring the effectiveness and safety of glucocorticoids in the treatment of COVID-19.

JAK-STAT inhibitors, like baricitinib, fedratinib, and ruxolitinib are potent anti-inflammatory drugs that are approved for rheumatoid arthritis and myelofibrosis. Patients infected with SARS-CoV-2 often present increased levels of pro-inflammatory cytokines and may benefit from the use of these drugs.

A case series reported clinical improvement in COVID-19 patients treated with baricitinib (103). These drugs are currently being tested in multiple randomized controlled trials.

Intravenous immunoglobulin (IVIg) may reduce SARS-CoV-2-induced inflammatory response by blocking FcR activation on monocytes. There are several clinical trials that Somapacitan-beco Injection (Sogroya)- FDA evaluate the efficacy and safety of IVIg therapy in patients with pneumonia caused by SARS-CoV-2. In a retrospective study of 58 COVID-19 patients, the use of IVIg within 48 h of admission increased in-hospital recovery and reduced Cortaid (Hydrocortisone Cream and Ointment 1.0%)- FDA interval fasting rate (95).

Mesenchymal stem cells (MSC) have immunomodulatory properties because they can inhibit T cell and macrophage activation and induce the formation of regulatory T cell and anti-inflammatory macrophages (121, 122). There is a pre-proof clinical trial that demonstrated Cortaid (Hydrocortisone Cream and Ointment 1.0%)- FDA efficacy of the MSC treatment in patients with ARDS secondary to Influenza A (H7N9) infection (124). Several ongoing clinical trials are testing the mesenchymal stem cells therapy against SARS-CoV-2.

Tocilizumab, a drug used to treat rheumatoid arthritis, is a monoclonal antibody against the IL-6 receptor. Since elevated IL-6 levels are commonly found in COVID-19, tocilizumab is now under evaluation by a multicenter randomized controlled trial (ChiCTR2000029765). The preliminary clinical results are encouraging (48). In an uncontrolled study of dentist teeth patients treated affected with severe COVID-19 infection, the use of tocilizumab improved symptoms and radiological findings (96).

Numerous other studies are ongoing to test this drug in patients affected by COVID-19. Cortaid (Hydrocortisone Cream and Ointment 1.0%)- FDA IL-6 inhibitors are being tested to treat COVID-19, including sarilumab and siltuximab. The latter showed a decrease in inflammatory markers in a study Cortaid (Hydrocortisone Cream and Ointment 1.0%)- FDA 21 COVID-19 patients (not peer-reviewed) (104).

Ulinastatin is a serin protease inhibitor with anti-inflammatory effects approved in China and Japan for the treatment of acute el sangre del diablo and sepsis (123). There is an ongoing clinical trial (NCT04393311) that is testing the safety and efficacy of ulinastatin compared to placebo in COVID-19 patients. Anakinra has been approved by the FDA for the treatment of rheumatoid arthritis and neonatal-onset multisystem inflammatory disease.

It is a recombinant human interleukin-1 receptor antagonist (IL-1Ra), and it is currently being tested in ongoing trials with COVID-19 patients to contrast the uncontrolled inflammatory response.

Experimental animal models showed that, although ACE inhibitors and ARBs do not directly affect ACE2 activity, these agents can upregulate the expression and activity of the receptor in heart and kidney tissue (127). These drugs are commonly prescribed for patients with diabetes or cardiovascular disease who have higher risk of severe COVID-19 disease which has raised concern for the use of these drugs during the infection (8).

However, the increased expression of ACE2 could limit the viral spread because it is not accompanied by an increase of TMPRSS2, so the virus sleep rem be tied to the receptor but could not enter the cells (8).

Experimental animal models of acute lung injury, including a model of SARS-CoV infection, showed that ARBs reduce Ang II-mediated lung damage and therefore attenuate COVID-19 infection (127). In a retrospective study of 6,272 patients with COVID-19 and matched COVID-19 negative controls, infected patients were associated with increased use of RAAS inhibitors, but these drugs did not correlate with a more severe disease after multivariable adjustment (105). The study by Reynolds et al.

The European and American Cardiology Societies, remarked that there is no evidence of a noxious effect of RAS inhibitors in patients affected by COVID-19 (128, 129). Moreover, discontinuation of RAS inhibitor both in healthy and infected individuals could lower dangerous, especially in high-risk patients, so personality psychologist suggest to maintain the ongoing therapy (130).

SARS-CoV-2 effects on the kidney and in patient with underlying kidney disease is not well-characterized. Preliminary data has indicated Kariva (Desogestrel and Ethinyl Estradiol and Ethinyl Estradiol)- Multum previous kidney disease could represent a Cortaid (Hydrocortisone Cream and Ointment 1.0%)- FDA factor, especially in elderly patients, for a more severe disease course.

SARS-CoV-2 infects the kidneys and may induce acute kidney injury. Further studies are necessary to better understand disease pathology, acute kidney injury associated with infection, long-term renal consequences, and potential therapies.

Rigorously controlled interventional studies and international registry analyses will be crucial to define risk factor and the best therapeutic approaches to resolving COVID-19 disease outcomes. CB wrote manuscript the initial draft. MW, GZ, and LR participated in the manuscript writing. PC supervised the manuscript.

The reviewer UM declared a past collaboration with one of the authors PC to the handling editor. McMichael TM, Currie DW, Clark S, Pogosjans S, Kay M, Schwartz NG, et al.

Epidemiology of Covid-19 in a long-term care facility in King County, Washington. Munster VJ, Koopmans M, van Doremalen Cortaid (Hydrocortisone Cream and Ointment 1.0%)- FDA, van Riel D, de Wit E. A novel coronavirus emerging in China - Key questions for impact assessment.

Velavan TP, Meyer CG. Trop Med Int Health. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated Cortaid (Hydrocortisone Cream and Ointment 1.0%)- FDA in-hospital death of patients with COVID-19. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al.



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